Buprenorphine

Identification

Summary

Buprenorphine is a partial opioid agonist used for management of severe pain that is not responsive to alternative treatments. Also used for maintenance treatment of opioid addiction.

Brand Names
Belbuca, Brixadi, Buprenex, Buprenorphine, Butrans, Sublocade, Suboxone, Subutex, Zubsolv
Generic Name
Buprenorphine
DrugBank Accession Number
DB00921
Background

Buprenorphine is a weak partial mu-opioid receptor agonist and a weak kappa-opioid receptor antagonist used for the treatment of severe pain.12,15 It is also commonly used as an alternative to methadone for the treatment of severe opioid addiction.22 Buprenorphine is commercially available as the brand name product Suboxone which is formulated in a 4:1 fixed-dose combination product along with naloxone, a non-selective competitive opioid receptor antagonist. Combination with naloxone is intended to reduce the abuse potential of Suboxone, as naloxone is poorly absorbed by the oral route (and has no effect when taken orally), but would reverse the opioid agonist effects of buprenorphine if injected intravenously.14,22 Buprenorphine has poor gastrointestinal absorption and is therefore formulated as a sublingual tablet.

Buprenorphine has a number of unique pharmacokinetic and pharmacodynamic properties that make it a preferred agent for the treatment of conditions requiring high doses of strong opioids.13 For example, buprenorphine dissociates from opioid receptors very slowly, resulting in a long duration of action and relief from pain or withdrawal symptoms for upwards of 24-36 hours. Use of once-daily buprenorphine may benefit individuals who have developed tolerance to other potent opioids and who require larger and more frequent doses. Buprenorphine may also be a preferred agent over methadone (which is also commonly used to treat severe pain and opioid use disorder), as it has less effect on Qtc interval prolongation,9,10 fewer drug interactions, reduced risk of sexual side effects,17 and an improved safety profile with a lower risk of overdose and respiratory depression.6,7,8

Buprenorphine acts as a partial mu-opioid receptor agonist with a high affinity for the receptor, but lower intrinsic activity compared to other full mu-opioid agonists such as heroin, oxycodone, or methadone.15 This means that buprenorphine preferentially binds the opioid receptor and displaces lower affinity opioids without activating the receptor to a comparable degree. Clinically, this results in a slow onset of action and a clinical phenomenon known as the "ceiling effect" where once a certain dose is reached, buprenorphine's effects plateau. This effect can be beneficial, however, as dose-related side effects such as respiratory depression, sedation, and intoxication also plateau at around 32mg, resulting in a lower risk of overdose compared to methadone and other full agonist opioids.4,5 It also means that opioid-dependent patients do not experience sedation or euphoria at the same rate that they might experience with more potent opioids, improving quality of life for patients with severe pain and reducing the reinforcing effects of opioids which can lead to drug-seeking behaviours.11

Treatment of opioid addiction with buprenorphine, methadone, or slow-release oral morphine (SROM) is termed Opioid Agonist Treatment (OAT) or Opioid Substitution Therapy (OST). The intention of substitution of illicit opioids with the long-acting opioids used in OAT is to prevent withdrawal symptomns for 24-36 hours following dosing to ultimately reduce cravings and drug-seeking behaviours. Use of OAT is also intended to improved social stabilization including a reduction in crime rates, marginalization, incarceration, and use of illicit substances such as heroin or fentanyl. Illegally purchased opioids can often be injected and may be laced with other substances that increase the risk of harm or overdose. Provision of OAT is often combined with education about harm reduction including use of clean needles and injection supplies in an effort to reduce the risks associated with injection drug use which includes contraction of HIV and Hepatitis C and other complications including skin infections, abscesses, or endocarditis.16

Type
Small Molecule
Groups
Approved, Illicit, Investigational, Vet approved
Structure
Weight
Average: 467.6401
Monoisotopic: 467.303558805
Chemical Formula
C29H41NO4
Synonyms
  • (−)-buprenorphine
  • 17-cyclopropylmethyl-4,5α-epoxy-7α-((S)-1-hydroxy-1,2,2-trimethylpropyl)-6-methoxy-6,14-endo-ethanomorphinan-3-ol
  • 2-(N-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-6-methoxy-6,14-endo-ethanomorphinan-6α-yl)-3,3-dimethyl-2-butanol
  • 2-[3-cyclopropylmethyl-11-hydroxy-15-methoxy-(14R)-13-oxa-3-azahexacyclo[13.2.2.12,8.01,6.06,14.07,12]icosa-7,9,11-trien-16-yl]-3,3-dimethyl-2-butanol
  • 21-cyclopropyl-7α-[(S)-1-hydroxy-1,2,2-trimethylpropyl]-6,14-endo-ethano-6,7,8,14-tetrahydrooripavine
  • Buprenophine
  • Buprenorfina
  • Buprenorphine
  • Buprenorphinum

Pharmacology

Indication

Buprenorphine is available in different formulations, such as sublingual tablets, buccal films, transdermal films, and injections, alone or in combination with naloxone.

The buccal film, intramuscular or intravenous injection, and transdermal formulation are indicated for the management of pain severe enough to require an opioid analgesic and for which alternate treatments are inadequate.21,23,24

The extended-release subcutaneous injections of buprenorphine are indicated for the treatment of moderate to severe opioid use disorder in patients who have initiated treatment with a single dose of a transmucosal buprenorphine product or who are already being treated with buprenorphine. Injections are part of a complete treatment plan that includes counselling and psychosocial support.20

Sublingual tablets and buccal films, in combination with naloxone, are indicated for the maintenance treatment of opioid dependence as part of a complete treatment plan that includes counselling and psychosocial support.19,22

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Used as adjunct in combination to treatOpioid dependenceCombination Product in combination with: Naloxone (DB01183)••••••••••••
Management ofSevere pain•••••••••••••••••••••
Adjunct therapy in treatment ofModerate opioid dependence•••••••••••••••••••••• ••••••••••• •••••••• •••••••
Management ofModerate pain•••••••••••••••••••••
Adjunct therapy in treatment ofSevere opioid dependence•••••••••••••••••••••• ••••••••••• •••••••• •••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

Buprenorphine interacts predominately with the opioid mu-receptor. These mu-binding sites are discretely distributed in the human brain, spinal cord, and other tissues. In clinical settings, buprenorphine exerts its principal pharmacologic effects on the central nervous system. Its primary actions of therapeutic value are analgesia and sedation. In addition to analgesia, alterations in mood, euphoria and dysphoria, and drowsiness commonly occur. Buprenorphine depresses the respiratory centers, depresses the cough reflex, and constricts the pupils.

Dependence

Buprenorphine is a partial agonist at the mu-opioid receptor and chronic administration produces physical dependence of the opioid type, characterized by withdrawal signs and symptoms upon abrupt discontinuation or rapid taper. The withdrawal syndrome is typically milder than seen with full agonists and may be delayed in onset. Buprenorphine can be abused in a manner similar to other opioids. This should be considered when prescribing or dispensing buprenorphine in situations when the clinician is concerned about an increased risk of misuse, abuse, or diversion.[F4718]

Withdrawal

Abrupt discontinuation of treatment is not recommended as it may result in an opioid withdrawal syndrome that may be delayed in onset. Signs and symptoms may include body aches, diarrhea, gooseflesh, loss of appetite, nausea, nervousness or restlessness, anxiety, runny nose, sneezing, tremors or shivering, stomach cramps, tachycardia, trouble with sleeping, unusual increase in sweating, palpitations, unexplained fever, weakness and yawning.[F4718]

Risk of Respiratory and Central Nervous System (CNS) Depression and Overdose

Buprenorphine has been associated with life-threatening respiratory depression and death. Many, but not all, post-marketing reports regarding coma and death involved misuse by self-injection or were associated with the concomitant use of buprenorphine and benzodiazepines or other CNS depressant, including alcohol. Use buprenorphine and naloxone sublingual tablets with caution in patients with compromised respiratory function (e.g., chronic obstructive pulmonary disease, cor pulmonale, decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression).22

Risk of Overdose in Opioid Naïve Patients

There have been reported deaths of opioid-naïve individuals who received a 2 mg dose of buprenorphine as a sublingual tablet for analgesia. Buprenorphine and naloxone sublingual tablets are not appropriate as an analgesic in opioid-naïve patients.22

Precipitation of Opioid Withdrawal Signs and Symptoms

If buprenorphine is started in opioid-dependent individuals, it will displace the other opioids and cause a phenomenon known as "precipitated withdrawal" which is characterized by a rapid and intense onset of withdrawal symptoms. Individuals must therefore be in a state of mild to moderate withdrawal before starting therapy with buprenorphine.

Because it contains naloxone, buprenorphine and naloxone sublingual tablets are also highly likely to produce marked and intense withdrawal signs and symptoms if misused parenterally by individuals dependent on full opioid agonists such as heroin, morphine, or methadone.22

Gastrointestinal Effects

Buprenorphine and other morphine-like opioids have been shown to decrease bowel motility and cause constipation. Buprenorphine may obscure the diagnosis or clinical course of patients with acute abdominal conditions and should be administered with caution to patients with dysfunction of the biliary tract.22

Effects on the Endocrine System

Opioids inhibit the secretion of adrenocorticotropic hormone (ACTH), cortisol, and luteinizing hormone (LH) in humans. They also stimulate prolactin, growth hormone (GH) secretion, and pancreatic secretion of insulin and glucagon. Chronic use of opioids may influence the hypothalamic-pituitary-gonadal axis, leading to androgen deficiency that may manifest as low libido, impotence, erectile dysfunction, amenorrhea, or infertility. The causal role of opioids in the clinical syndrome of hypogonadism is unknown because the various medical, physical, lifestyle, and psychological stressors that may influence gonadal hormone levels have not been adequately controlled for in studies conducted to date. Patients presenting with symptoms of androgen deficiency should undergo laboratory evaluation.22

Adrenal Insufficiency

Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use. Presentation of adrenal insufficiency may include non-specific symptoms and signs including nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure. If adrenal insufficiency is suspected, confirm the diagnosis with diagnostic testing as soon as possible. If adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids. Wean the patient off of the opioid to allow adrenal function to recover and continue corticosteroid treatment until adrenal function recovers. Other opioids may be tried as some cases reported use of a different opioid without recurrence of adrenal insufficiency. The information available does not identify any particular opioids as being more likely to be associated with adrenal insufficiency.22

Use in Patients With Impaired Hepatic Function

Buprenorphine/naloxone products are not recommended in patients with severe hepatic impairment and may not be appropriate for patients with moderate hepatic impairment. The doses of buprenorphine and naloxone in this fixed-dose combination product cannot be individually titrated, and hepatic impairment results in a reduced clearance of naloxone to a much greater extent than buprenorphine. Therefore, patients with severe hepatic impairment will be exposed to substantially higher levels of naloxone than patients with normal hepatic function. This may result in an increased risk of precipitated withdrawal at the beginning of treatment (induction) and may interfere with buprenorphine’s efficacy throughout treatment. In patients with moderate hepatic impairment, the differential reduction of naloxone clearance compared to buprenorphine clearance is not as great as in subjects with severe hepatic impairment. However, buprenorphine/naloxone products are not recommended for initiation of (treatment induction) in patients with moderate hepatic impairment due to the increased risk of precipitated withdrawal. Buprenorphine/naloxone products may be used with caution for maintenance treatment in patients with moderate hepatic impairment who have initiated treatment on a buprenorphine product without naloxone. However, patients should be carefully monitored and consideration given to the possibility of naloxone interfering with buprenorphine’s efficacy.22

Risk of Hepatitis, Hepatic Events

Cases of cytolytic hepatitis and hepatitis with jaundice have been observed in individuals receiving buprenorphine in clinical trials and through post-marketing adverse event reports. The spectrum of abnormalities ranges from transient asymptomatic elevations in hepatic transaminases to case reports of death, hepatic failure, hepatic necrosis, hepatorenal syndrome, and hepatic encephalopathy. In many cases, the presence of pre-existing liver enzyme abnormalities, infection with hepatitis B or hepatitis C virus, concomitant usage of other potentially hepatotoxic drugs, and ongoing injecting drug use may have played a causative or contributory role. In other cases, insufficient data were available to determine the etiology of the abnormality. Withdrawal of buprenorphine has resulted in amelioration of acute hepatitis in some cases; however, in other cases no dose reduction was necessary. The possibility exists that buprenorphine had a causative or contributory role in the development of the hepatic abnormality in some cases. Liver function tests, prior to initiation of treatment is recommended to establish a baseline. Periodic monitoring of liver function during treatment is also recommended. A biological and etiological evaluation is recommended when a hepatic event is suspected. Depending on the case, buprenorphine and naloxone sublingual tablets may need to be carefully discontinued to prevent withdrawal signs and symptoms and a return by the patient to illicit drug use, and strict monitoring of the patient should be initiated.22

Orthostatic Hypotension

Like other opioids, buprenorphine and naloxone sublingual tablets may produce orthostatic hypotension in ambulatory patients.

Elevation of Cerebrospinal Fluid Pressure

Buprenorphine, like other opioids, may elevate cerebrospinal fluid pressure and should be used with caution in patients with head injury, intracranial lesions, and other circumstances when cerebrospinal pressure may be increased. Buprenorphine can produce miosis and changes in the level of consciousness that may interfere with patient evaluation.

Elevation of Intracholedochal Pressure

Buprenorphine has been shown to increase intracholedochal pressure, as do other opioids, and thus should be administered with caution to patients with dysfunction of the biliary tract.

Mechanism of action

Buprenorphine is a partial agonist at the mu-opioid receptor and an antagonist at the kappa-opioid receptor. It demonstrates a high affinity for the mu-opioid receptor but has lower intrinsic activity compared to other full mu-opioid agonists such as heroin, oxycodone, or methadone.15 This means that buprenorphine preferentially binds the opioid receptor and displaces lower affinity opioids without activating the receptor to a comparable degree. Clinically, this results in a slow onset of action and a clinical phenomenon known as the "ceiling effect" where once a certain dose is reached buprenorphine's effects plateau. This effect can be beneficial, however, as dose-related side effects such as respiratory depression, sedation, and intoxication also plateau at around 32mg, resulting in a lower risk of overdose compared to methadone and other full agonist opioids.4,5 It also means that opioid-dependent patients do not experience sedation or euphoria at the same rate that they might experience with more potent opioids, improving quality of life for patients with severe pain and reducing the reinforcing effects of opioids which can lead to drug-seeking behaviours.11

Buprenorphine's high affinity, but low intrinsic activity for the mu-opioid receptor also means that if it is started in opioid-dependent individuals, it will displace the other opioids without creating an equal opioid effect and cause a phenomenon known as "precipitated withdrawal" which is characterized by a rapid and intense onset of withdrawal symptoms (i.e. anxiety, restlessness, gastrointestinal distress, diaphoresis, intense drug cravings, and tachycardia). Individuals must therefore be in a state of mild to moderate withdrawal before starting therapy with buprenorphine.

Buprenorphine is commercially available as the brand name product Suboxone which is formulated in a 4:1 fixed-dose combination product along with naloxone, a non-selective competitive opioid receptor antagonist. Combination of an opioid agonist with an opioid antagonist may seem counterintuitive, however this combination with naloxone is intended to reduce the abuse potential of Suboxone, as naloxone is poorly absorbed by the oral route (and has no effect when taken orally), but would reverse the opioid agonist effects of buprenorphine if injected intravenously.14,22

TargetActionsOrganism
AKappa-type opioid receptor
antagonist
Humans
AMu-type opioid receptor
partial agonist
Humans
UDelta-type opioid receptor
antagonist
Humans
UNociceptin receptorNot AvailableHumans
Absorption

Bioavailablity of buprenorphine/naloxone is very high following intravenous or subcutaneous administration, lower by the sublingual or buccal route, and very low when administered by the oral route. It is therefore provided as a sublingual tablet that is absorbed from the oral mucosa directly into systemic circulation.18

Clinical pharmacokinetic studies found that there was wide inter-patient variability in the sublingual absorption of buprenorphine and naloxone, but within subjects the variability was low. Both Cmax and AUC of buprenorphine increased in a linear fashion with the increase in dose (in the range of 4 to 16 mg), although the increase was not directly dose-proportional. Buprenorphine combination with naloxone (2mg/0.5mg) provided in sublingual tablets demonstrated a Cmax of 0.780 ng/mL with a Tmax of 1.50 hr and AUC of 7.651 ng.hr/mL.22

Coadministration with naloxone does not effect the pharmacokinetics of buprenorphine.

Volume of distribution

Buprenorphine is highly lipophilic, and therefore extensively distributed, with rapid penetration through the blood-brain barrier. The estimated volume of distribution is 188 - 335 L when given intravenously. It is able to cross into the placenta and breast milk.

Protein binding

Buprenorphine is approximately 96% protein-bound, primarily to alpha- and beta-globulin.22

Metabolism

Buprenorphine is metabolized to norbuprenorphine via Cytochrome P450 3A4/3A5-mediated N-dealkylation. Buprenorphine and norbuprenorphine both also undergo glucuronidation to the inactive metabolites buprenorphine-3-glucuronide and norbuprenorphine-3-glucuronide, respectively.18,22

While norbuprenorphine has been found to bind to opioid receptors in-vitro, brain concentrations are very low which suggests that it does not contribute to the clinical effects of buprenorphine.18

Naloxone undergoes direct glucuronidation to naloxone-3-glucuronide as well as N-dealkylation, and reduction of the 6-oxo group.22

Hover over products below to view reaction partners

Route of elimination

Buprenorphine, like morphine and other phenolic opioid analgesics, is metabolized by the liver and its clearance is related to hepatic blood flow. It is primarily eliminated via feces (as free forms of buprenorphine and norbuprenorphine) while 10 - 30% of the dose is excreted in urine (as conjugated forms of buprenorphine and norbuprenorphine).22

The overall mean elimination half-life of buprenorphine in plasma ranges from 31 to 42 hours, although the levels are very low 10 hours after dosing (majority of AUC of buprenorphine is captured within 10 hours), indicating that the effective half-life may be shorter.22

Half-life

Buprenorphine demonstrates slow dissociation kinetics (~166 min), which contributes to its long duration of action and allows for once-daily or even every-second-day dosing.18 In clinical trial studies, the half-life of sublingually administered buprenorphine/naloxone 2mg/0.5mg was found to be 30.75 hours.22

Clearance

Clearance may be higher in children than in adults. Plasma clearance rate, IV administration, anaesthetized patients = 901.2 ± 39.7 mL/min; Plasma clearance rate, IV administration, healthy subjects = 1042 - 1280 mL/min.

Adverse Effects
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Toxicity

Manifestations of acute overdose include pinpoint pupils, sedation, hypotension, respiratory depression and death.

Pathways
PathwayCategory
Buprenorphine Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
1,2-Benzodiazepine1,2-Benzodiazepine may increase the central nervous system depressant (CNS depressant) activities of Buprenorphine.
AbametapirThe serum concentration of Buprenorphine can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Buprenorphine can be increased when combined with Abatacept.
AbemaciclibThe metabolism of Abemaciclib can be decreased when combined with Buprenorphine.
AbirateroneThe metabolism of Buprenorphine can be decreased when combined with Abiraterone.
Food Interactions
  • Avoid alcohol. Ingesting alcohol may increase the sedative and CNS depressant effects of buprenorphine.
  • Avoid grapefruit products. Grapefruit inhibits the metabolism of buprenorphine through CYP3A4, which increases the serum levels buprenorphine.
  • Take separate from meals. When buprenorphine is formulated as a sublingual tablet or buccal film, avoid eating or drinking until the dosage form is completely dissolved.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Buprenorphine hydrochloride56W8MW3EN153152-21-9UAIXRPCCYXNJMQ-RZIPZOSSSA-N
Product Images
International/Other Brands
Addnok (Rusan Pharma Ltd.) / Buprel / Buprigesic (Neon Laboratories) / Morgesic (Samarth Pharma) / Norphin (Unichem Laboratories) / Norspan / Temgesic / Tidigesic (Sun Pharmaceuticals)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
BelbucaFilm300 ug/1BuccalEndo Pharmaceuticals2015-06-012019-06-30US flag
BelbucaFilm, soluble150 ug/1BuccalBioDelivery Sciences International Inc2017-10-01Not applicableUS flag
BelbucaFilm, soluble750 mcgBuccalPurdue PharmaNot applicableNot applicableCanada flag
BelbucaFilm, soluble150 mcgBuccalPurdue Pharma2018-01-172019-05-31Canada flag
BelbucaFilm, soluble450 ug/1BuccalBioDelivery Sciences International Inc2017-08-21Not applicableUS flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Bar-buprenorphinePatch10 mcg / hourTransdermalBard Pharmaceuticals (1990) IncNot applicableNot applicableCanada flag
Bar-buprenorphinePatch20 mcg / hourTransdermalBard Pharmaceuticals (1990) IncNot applicableNot applicableCanada flag
Bar-buprenorphinePatch5 mcg / hourTransdermalBard Pharmaceuticals (1990) IncNot applicableNot applicableCanada flag
Bar-buprenorphinePatch15 mcg / hourTransdermalBard Pharmaceuticals (1990) IncNot applicableNot applicableCanada flag
BuprenorphenePatch, extended release15 ug/1hTransdermalApotex Corporation2021-10-01Not applicableUS flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
BunavailBuprenorphine hydrochloride (6.3 mg/1) + Naloxone hydrochloride dihydrate (1 mg/1)FilmBuccalBioDelivery Sciences International Inc2014-09-302021-07-31US flag
BunavailBuprenorphine hydrochloride (4.2 mg/1) + Naloxone hydrochloride dihydrate (0.7 mg/1)FilmBuccalBioDelivery Sciences International Inc2014-09-302021-10-31US flag
BunavailBuprenorphine hydrochloride (2.1 mg/1) + Naloxone hydrochloride dihydrate (0.3 mg/1)FilmBuccalBioDelivery Sciences International Inc2014-09-302021-02-28US flag
Bupensan Duo 2 mg/0,5 mg-SublingualtablettenBuprenorphine hydrochloride (2 mg) + Naloxone hydrochloride dihydrate (0.5 mg)Tablet, orally disintegratingSublingualG.L. Pharma Gmb H2018-06-06Not applicableAustria flag
Bupensan Duo 4 mg/1 mg-SublingualtablettenBuprenorphine hydrochloride (4 mg) + Naloxone hydrochloride dihydrate (1 mg)Tablet, orally disintegratingSublingualG.L. Pharma Gmb H2018-06-06Not applicableAustria flag

Categories

ATC Codes
N07BC01 — BuprenorphineN07BC51 — Buprenorphine, combinationsN02AE01 — Buprenorphine
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as phenanthrenes and derivatives. These are polycyclic compounds containing a phenanthrene moiety, which is a tricyclic aromatic compound with three non-linearly fused benzene.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Phenanthrenes and derivatives
Sub Class
Not Available
Direct Parent
Phenanthrenes and derivatives
Alternative Parents
Tetralins / Azaspirodecane derivatives / Coumarans / Aralkylamines / Alkyl aryl ethers / 1-hydroxy-2-unsubstituted benzenoids / Piperidines / Tertiary alcohols / Trialkylamines / Oxacyclic compounds
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Substituents
1-hydroxy-2-unsubstituted benzenoid / Alcohol / Alkyl aryl ether / Amine / Aralkylamine / Aromatic heteropolycyclic compound / Azacycle / Azaspirodecane / Coumaran / Dialkyl ether
show 15 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
morphinane alkaloid (CHEBI:3216)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
40D3SCR4GZ
CAS number
52485-79-7
InChI Key
RMRJXGBAOAMLHD-IHFGGWKQSA-N
InChI
InChI=1S/C29H41NO4/c1-25(2,3)26(4,32)20-15-27-10-11-29(20,33-5)24-28(27)12-13-30(16-17-6-7-17)21(27)14-18-8-9-19(31)23(34-24)22(18)28/h8-9,17,20-21,24,31-32H,6-7,10-16H2,1-5H3/t20-,21-,24-,26+,27-,28+,29-/m1/s1
IUPAC Name
(1S,2R,6S,14R,15R,16R)-3-(cyclopropylmethyl)-16-[(2S)-2-hydroxy-3,3-dimethylbutan-2-yl]-15-methoxy-13-oxa-3-azahexacyclo[13.2.2.1^{2,8}.0^{1,6}.0^{6,14}.0^{7,12}]icosa-7,9,11-trien-11-ol
SMILES
CO[C@]12CC[C@@]3(C[C@@H]1[C@](C)(O)C(C)(C)C)[C@H]1CC4=C5C(O[C@@H]2[C@@]35CCN1CC1CC1)=C(O)C=C4

References

Synthesis Reference

Kazuhisa Ninomiya, Yasuhiro Fukushima, Mutsuo Okumura, Yuko Hosokawa, "Buprenorphine percutaneous absorption preparation." U.S. Patent US6090405, issued August, 1992.

US6090405
General References
  1. Huang P, Kehner GB, Cowan A, Liu-Chen LY: Comparison of pharmacological activities of buprenorphine and norbuprenorphine: norbuprenorphine is a potent opioid agonist. J Pharmacol Exp Ther. 2001 May;297(2):688-95. [Article]
  2. Bodkin JA, Zornberg GL, Lukas SE, Cole JO: Buprenorphine treatment of refractory depression. J Clin Psychopharmacol. 1995 Feb;15(1):49-57. [Article]
  3. Elkader A, Sproule B: Buprenorphine: clinical pharmacokinetics in the treatment of opioid dependence. Clin Pharmacokinet. 2005;44(7):661-80. [Article]
  4. Dahan A, Yassen A, Bijl H, Romberg R, Sarton E, Teppema L, Olofsen E, Danhof M: Comparison of the respiratory effects of intravenous buprenorphine and fentanyl in humans and rats. Br J Anaesth. 2005 Jun;94(6):825-34. doi: 10.1093/bja/aei145. Epub 2005 Apr 15. [Article]
  5. Walsh SL, Preston KL, Stitzer ML, Cone EJ, Bigelow GE: Clinical pharmacology of buprenorphine: ceiling effects at high doses. Clin Pharmacol Ther. 1994 May;55(5):569-80. doi: 10.1038/clpt.1994.71. [Article]
  6. Bruneau J, Ahamad K, Goyer ME, Poulin G, Selby P, Fischer B, Wild TC, Wood E: Management of opioid use disorders: a national clinical practice guideline. CMAJ. 2018 Mar 5;190(9):E247-E257. doi: 10.1503/cmaj.170958. [Article]
  7. Luty J, O'Gara C, Sessay M: Is methadone too dangerous for opiate addiction? BMJ. 2005 Dec 10;331(7529):1352-3. doi: 10.1136/bmj.331.7529.1352. [Article]
  8. Marteau D, McDonald R, Patel K: The relative risk of fatal poisoning by methadone or buprenorphine within the wider population of England and Wales. BMJ Open. 2015 May 29;5(5):e007629. doi: 10.1136/bmjopen-2015-007629. [Article]
  9. Wedam EF, Bigelow GE, Johnson RE, Nuzzo PA, Haigney MC: QT-interval effects of methadone, levomethadyl, and buprenorphine in a randomized trial. Arch Intern Med. 2007 Dec 10;167(22):2469-75. doi: 10.1001/archinte.167.22.2469. [Article]
  10. Anchersen K, Clausen T, Gossop M, Hansteen V, Waal H: Prevalence and clinical relevance of corrected QT interval prolongation during methadone and buprenorphine treatment: a mortality assessment study. Addiction. 2009 Jun;104(6):993-9. doi: 10.1111/j.1360-0443.2009.02549.x. Epub 2009 Apr 9. [Article]
  11. Tzschentke TM: Behavioral pharmacology of buprenorphine, with a focus on preclinical models of reward and addiction. Psychopharmacology (Berl). 2002 Apr;161(1):1-16. doi: 10.1007/s00213-002-1003-8. Epub 2002 Mar 6. [Article]
  12. Lutfy K, Eitan S, Bryant CD, Yang YC, Saliminejad N, Walwyn W, Kieffer BL, Takeshima H, Carroll FI, Maidment NT, Evans CJ: Buprenorphine-induced antinociception is mediated by mu-opioid receptors and compromised by concomitant activation of opioid receptor-like receptors. J Neurosci. 2003 Nov 12;23(32):10331-7. [Article]
  13. Johnson RE, Strain EC, Amass L: Buprenorphine: how to use it right. Drug Alcohol Depend. 2003 May 21;70(2 Suppl):S59-77. doi: 10.1016/s0376-8716(03)00060-7. [Article]
  14. Orman JS, Keating GM: Buprenorphine/naloxone: a review of its use in the treatment of opioid dependence. Drugs. 2009;69(5):577-607. doi: 10.2165/00003495-200969050-00006. [Article]
  15. Lutfy K, Cowan A: Buprenorphine: a unique drug with complex pharmacology. Curr Neuropharmacol. 2004 Oct;2(4):395-402. doi: 10.2174/1570159043359477. [Article]
  16. Toce MS, Chai PR, Burns MM, Boyer EW: Pharmacologic Treatment of Opioid Use Disorder: a Review of Pharmacotherapy, Adjuncts, and Toxicity. J Med Toxicol. 2018 Dec;14(4):306-322. doi: 10.1007/s13181-018-0685-1. Epub 2018 Oct 30. [Article]
  17. Yee A, Loh HS, Hisham Hashim HM, Ng CG: Clinical factors associated with sexual dysfunction among men in methadone maintenance treatment and buprenorphine maintenance treatment: a meta-analysis study. Int J Impot Res. 2014 Sep-Oct;26(5):161-6. doi: 10.1038/ijir.2014.18. Epub 2014 Jul 3. [Article]
  18. Coe MA, Lofwall MR, Walsh SL: Buprenorphine Pharmacology Review: Update on Transmucosal and Long-acting Formulations. J Addict Med. 2019 Mar/Apr;13(2):93-103. doi: 10.1097/ADM.0000000000000457. [Article]
  19. FDA Approved Drug Products: Bunavail (buprenorphine and naloxone) Sublingual, Buccal Film [Link]
  20. FDA Approved Drug Products: BRIXADI (buprenorphine) extended-release injection for subcutaneous use CIII (May 2023) [Link]
  21. FDA Approved Drug Products: BUPRENEX (buprenorphine hydrochloride) injection, for intravenous or intramuscular administration, CIII (June 2022) [Link]
  22. FDA Approved Drug Products: SUBOXONE (buprenorphine and naloxone) sublingual tablets, CIII (June 2022) [Link]
  23. FDA Approved Drug Products: BELBUCA (buprenorphine buccal film), CIII (June 2022) [Link]
  24. FDA Approved Drug Products: BUTRANS (buprenorphine) transdermal system, CIII (June 2022) [Link]
  25. FDA Approved Drug Products: SUBLOCADE (buprenorphine extended‐release) injection, for subcutaneous use, CIII (December 2023) [Link]
Human Metabolome Database
HMDB0015057
KEGG Drug
D07132
KEGG Compound
C08007
PubChem Compound
644073
PubChem Substance
46505782
ChemSpider
559124
BindingDB
50026603
RxNav
1819
ChEBI
3216
ChEMBL
CHEMBL560511
ZINC
ZINC000001319780
Therapeutic Targets Database
DAP001353
PharmGKB
PA448685
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Buprenorphine
FDA label
Download (345 KB)
MSDS
Download (196 KB)

Clinical Trials

Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package
PhaseStatusPurposeConditionsCountStart DateWhy Stopped100+ additional columns
Not AvailableCompletedNot AvailableAcquired Immune Deficiency Syndrome (AIDS) / Human Immunodeficiency Virus (HIV) Infections / Opiate Addiction / Substance Dependence1somestatusstop reasonjust information to hide
Not AvailableCompletedNot AvailableAcquired Immune Deficiency Syndrome (AIDS) / Human Immunodeficiency Virus (HIV) Infections / Opiate Dependence / Post Traumatic Stress Disorder (PTSD)1somestatusstop reasonjust information to hide
Not AvailableCompletedNot AvailableBuprenorphine / Naloxone / Opiate Dependence / Opiate-Related Disorders / Substance Abuse1somestatusstop reasonjust information to hide
Not AvailableCompletedNot AvailableCancer1somestatusstop reasonjust information to hide
Not AvailableCompletedNot AvailableCancer Pain / Cancer Related Pain (Breakthrough Pain) / Neuropathic Pain / Tumor1somestatusstop reasonjust information to hide

Pharmacoeconomics

Manufacturers
  • Purdue pharma lp
  • Reckitt benckiser pharmaceuticals inc
  • Bedford laboratories div ben venue laboratories inc
  • Hospira inc
  • Pharmaforce inc
  • Barr laboratories inc
  • Roxane laboratories inc
Packagers
  • A-S Medication Solutions LLC
  • Bedford Labs
  • Ben Venue Laboratories Inc.
  • Bryant Ranch Prepack
  • Hospira Inc.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Pharmaforce Inc.
  • Prepak Systems Inc.
  • Purdue Pharma LP
  • Rebel Distributors Corp.
  • Reckitt Benckiser Inc.
  • Remedy Repack
  • Roxane Labs
  • Teva Pharmaceutical Industries Ltd.
Dosage Forms
FormRouteStrength
PlasterTransdermal35 Mikrogramm/h
PlasterTransdermal52.5 Mikrogramm/h
PlasterTransdermal70 Mikrogramm/h
FilmBuccal150 ug/1
FilmBuccal300 ug/1
FilmBuccal450 ug/1
FilmBuccal600 ug/1
FilmBuccal75 ug/1
FilmBuccal750 ug/1
FilmBuccal900 ug/1
Film, solubleBuccal150 mcg
Film, solubleBuccal150 ug/1
Film, solubleBuccal300 mcg
Film, solubleBuccal300 ug/1
Film, solubleBuccal450 ug/1
Film, solubleBuccal450 mcg
Film, solubleBuccal600 ug/1
Film, solubleBuccal600 mcg
Film, solubleBuccal75 ug/1
Film, solubleBuccal75 mcg
Film, solubleBuccal750 ug/1
Film, solubleBuccal750 mcg
Film, solubleBuccal900 mcg
Film, solubleBuccal900 ug/1
SolutionParenteral
InjectionSubcutaneous128 mg/0.36mL
InjectionSubcutaneous16 mg/0.32mL
InjectionSubcutaneous24 mg/0.48mL
InjectionSubcutaneous32 mg/0.64mL
InjectionSubcutaneous64 mg/0.18mL
InjectionSubcutaneous8 mg/0.16mL
InjectionSubcutaneous96 mg/0.27mL
TabletOral0.216 mg
FilmBuccal
PlasterTransdermal
Tablet, orally disintegratingSublingual1 mg
Tablet, orally disintegratingSublingual12 mg
Tablet, orally disintegratingSublingual16 mg
Tablet, orally disintegratingSublingual2 MG
Tablet, orally disintegratingSublingual4 MG
Tablet, orally disintegratingSublingual8 MG
PlasterCutaneous52.5 UG
PlasterCutaneous5 UG
PlasterCutaneous10 UG
PlasterCutaneous15 UG
PlasterCutaneous20 UG
PlasterCutaneous35 UG
PlasterCutaneous70 UG
Tablet, orally disintegratingSublingual0.4 MG
Tablet
PlasterCutaneous30 UG
PlasterCutaneous40 UG
PlasterCutaneous35 mcg/1
PlasterCutaneous70 mcg/1
PlasterTransdermal10 Mikrogramm/h
PlasterTransdermal20 Mikrogramm/h
PlasterTransdermal5 Mikrogramm/h
Tablet, orally disintegratingSublingual0.2 MG
PatchTransdermal10 ug/1h
PatchTransdermal15 ug/1h
PatchTransdermal20 ug/1h
PatchTransdermal5 ug/1h
PatchTransdermal7.5 ug/1h
Patch, extended releaseTransdermal15 ug/1h
FilmBuccal; Sublingual
Film, solubleBuccal; Sublingual
InjectionIntramuscular; Intravenous0.3 mg/1mL
InjectionIntramuscular; Intravenous0.324 mg/1mL
Injection, solutionIntramuscular; Intravenous0.3 mg/1mL
Injection, solutionIntramuscular; Intravenous0.324 mg/1mL
PowderNot applicable1 kg/1kg
TabletOral2 mg/1
TabletOral8 mg/1
TabletSublingual2 mg/1
TabletSublingual8 mg/1
PatchTransdermal35 Mikrogramm/h
PatchTransdermal52.5 Mikrogramm/h
PatchTransdermal70 Mikrogramm/h
PatchTransdermal25 MICROGRAMMI/H
PatchTransdermal30 MICROGRAMMI/H
PatchTransdermal40 MICROGRAMMI/H
PatchTransdermal10 mcg
PatchTransdermal15 mcg
PatchTransdermal20 mcg
PatchTransdermal5 mcg
Patch, extended releaseTransdermal10 ug/1h
Patch, extended releaseTransdermal2.5 ug/1h
Patch, extended releaseTransdermal20 ug/1h
Patch, extended releaseTransdermal5 ug/1h
Patch, extended releaseTransdermal7.5 ug/1h
PatchTransdermal10 mcg / hour
PlasterCutaneous10 MIKROGRAMM
PatchTransdermal15 mcg / hour
PatchTransdermal20 mcg / hour
PlasterCutaneous20 MIKROGRAMM
PatchTransdermal5 mcg / hour
PlasterCutaneous5 MIKROGRAMM
Injection, suspension, extended releaseSubcutaneous128 MG
Injection, suspension, extended releaseSubcutaneous16 MG
Injection, suspension, extended releaseSubcutaneous160 MG
Injection, suspension, extended releaseSubcutaneous24 MG
Injection, suspension, extended releaseSubcutaneous32 MG
Injection, suspension, extended releaseSubcutaneous64 MG
Injection, suspension, extended releaseSubcutaneous8 MG
Injection, suspension, extended releaseSubcutaneous96 MG
PatchTransdermal40.000 mg
PatchTransdermal35 mcg
PatchTransdermal52.5 mcg
PatchTransdermal70 mcg
TabletOral
TabletSublingual0.2 mg
PlasterTransdermal10 Mikrogramm/Stunde
PlasterCutaneous10 mg
PlasterTransdermal20 Mikrogramm/Stunde
PlasterCutaneous30 MIKROGRAMM
PlasterCutaneous40 MIKROGRAMM
PlasterTransdermal5 Mikrogramm/Stunde
PlasterCutaneous5 mg
SolutionTransdermal20 mg/patch
SolutionTransdermal5 mg
SolutionTransdermal10 mg
PatchTransdermal10 MICROGRAMMI/ORA
PatchTransdermal15 MICROGRAMMI/ORA
PatchTransdermal20 MICROGRAMMI/ORA
PatchTransdermal25 MICROGRAMMI/ORA
PatchTransdermal30 MICROGRAMMI/ORA
PatchTransdermal40 MICROGRAMMI/ORA
PatchTransdermal5 MICROGRAMMI/ORA
SolutionParenteral0.323 mg
Tablet2 MG
Tablet8 MG
ImplantSubcutaneous80 mg
ImplantSubcutaneous80 mg/1
PatchTransdermal10 MICROGRAMMI/H
PatchTransdermal20 MICROGRAMMI/H
PatchTransdermal5 MICROGRAMMI/H
ImplantSubcutaneous74.2 MG
PatchTransdermal10.000 mg
PatchTransdermal10 mcg/h
PatchTransdermal5 mcg/h
Patch, extended releaseTransdermal10.0 mg
Patch, extended releaseTransdermal20.0 mg
Patch, extended releaseTransdermal5.0 mg
SolutionSubcutaneous100 mg/1
SolutionSubcutaneous300 mg/1
Solution, gel forming, extended releaseSubcutaneous100 mg / 0.5 mL
Solution, gel forming, extended releaseSubcutaneous300 mg / 1.5 mL
Film, solubleSublingual
TabletOral
TabletOral; Sublingual
TabletSublingual
Tablet, orally disintegratingSublingual2.16 MG
Tablet, orally disintegratingSublingual8.64 MG
FilmSublingual
Injection, suspension, extended releaseSubcutaneous100 MG
Injection, suspension, extended releaseSubcutaneous300 MG
TabletOral0.4 mg
TabletOral2 mg
TabletOral8 mg
SolutionParenteral0.300 mg
Injection, solutionParenteral0.3 MG/ML
Tablet0.2 MG
Tablet4 MG
Injection, solutionParenteral0.3 mg
InjectionIntramuscular; Intravenous0.3 mg/ml
InjectionIntramuscular0.3 MG/ML
TabletOral0.2 mg
PatchTransdermal30.000 mg
PatchTransdermal35 mcg/h
PatchTransdermal52.5 mcg/h
PatchTransdermal70 mcg/h
PlasterCutaneous35 MIKROGRAMM
PlasterCutaneous35 mcg/h
PlasterCutaneous52.5 MIKROGRAMM
PlasterCutaneous52.5 mcg/h
PlasterCutaneous70 MIKROGRAMM
PlasterCutaneous70 mcg/h
PlasterCutaneous20 MG
PlasterCutaneous40 MG
PlasterCutaneous30 MG
SolutionTransdermal20 mg
SolutionTransdermal30 mg
SolutionTransdermal40 mg
PatchTransdermal
PatchTransdermal35 MICROGRAMMI/H
PatchTransdermal52.5 MICROGRAMMI/H
PatchTransdermal70 MICROGRAMMI/H
Tablet, orally disintegratingSublingual
Prices
Unit descriptionCostUnit
Buprenex 0.3 mg/ml Solution (1 Box Contains Five 1ml Box)46.39USD box
Subutex 8 mg Sublingual Tabs10.2USD tab
Subutex 8 mg tablet sl9.4USD tablet
Buprenorphine 8 mg tablet sl7.74USD tablet
Buprenex 0.3 mg/ml ampul6.96USD ml
Subutex 2 mg Sublingual Tabs5.59USD tab
Subutex 2 mg tablet sl5.0USD tablet
Buprenorphine 2 mg tablet sl4.14USD tablet
Buprenorphine 0.3 mg/ml vial2.96USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US5968547No1999-10-192017-09-29US flag
US5240711No1993-08-312010-11-28US flag
CA2276170No2007-12-042018-02-24Canada flag
CA2030178No1995-08-152010-11-16Canada flag
US6344211No2002-02-052015-12-18US flag
USRE41489No2010-08-102017-09-29US flag
USRE41408No2010-06-292017-09-29US flag
USRE41571No2010-08-242017-09-29US flag
US6264980No2001-07-242015-12-18US flag
US7579019No2009-08-252020-01-22US flag
US6159498No2000-12-122016-10-18US flag
US8475832No2013-07-022030-03-26US flag
US8603514No2013-12-102024-04-03US flag
US8017150No2011-09-132023-02-13US flag
US8147866No2012-04-032027-07-23US flag
US8703177No2014-04-222032-08-20US flag
US8470361No2013-06-252030-05-22US flag
US8454996No2013-06-042019-09-24US flag
US8658198No2014-02-252027-12-03US flag
US8940330No2015-01-272032-09-18US flag
US9259421No2016-02-162032-09-18US flag
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US9498432No2016-11-222031-06-06US flag
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US9272044No2016-03-012031-06-06US flag
US8975270No2015-03-102031-09-05US flag
US8921387No2014-12-302032-01-06US flag
US9855221No2018-01-022022-02-14US flag
US9901539No2018-02-272032-12-21US flag
US9931305No2018-04-032022-02-14US flag
US10198218No2019-02-052031-06-06US flag
US10285910No2019-05-142022-10-11US flag
US10558394No2020-02-112031-06-25US flag
US10592168No2020-03-172031-06-06US flag
US10646484No2020-05-122038-06-22US flag
US10874661No2020-12-292032-09-18US flag
US10946010No2021-03-162032-09-18US flag
US11000520No2021-05-112035-11-06US flag
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US8236292No2012-08-072027-01-10US flag
US11135215No2021-10-052032-07-26US flag
US11839611No2015-11-062035-11-06US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
logP4.98AVDEEF,A ET AL. (1996)
pKa8.31 (at 25 °C)AVDEEF,A ET AL. (1996)
Predicted Properties
PropertyValueSource
Water Solubility0.0168 mg/mLALOGPS
logP4.53ALOGPS
logP3.55Chemaxon
logS-4.4ALOGPS
pKa (Strongest Acidic)10.42Chemaxon
pKa (Strongest Basic)9.63Chemaxon
Physiological Charge1Chemaxon
Hydrogen Acceptor Count5Chemaxon
Hydrogen Donor Count2Chemaxon
Polar Surface Area62.16 Å2Chemaxon
Rotatable Bond Count5Chemaxon
Refractivity131.76 m3·mol-1Chemaxon
Polarizability53.03 Å3Chemaxon
Number of Rings7Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterNoChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9055
Blood Brain Barrier+0.9401
Caco-2 permeable+0.6893
P-glycoprotein substrateSubstrate0.9126
P-glycoprotein inhibitor IInhibitor0.5192
P-glycoprotein inhibitor IINon-inhibitor0.6992
Renal organic cation transporterInhibitor0.5797
CYP450 2C9 substrateNon-substrate0.8366
CYP450 2D6 substrateSubstrate0.8919
CYP450 3A4 substrateSubstrate0.8142
CYP450 1A2 substrateNon-inhibitor0.9153
CYP450 2C9 inhibitorNon-inhibitor0.8692
CYP450 2D6 inhibitorNon-inhibitor0.6721
CYP450 2C19 inhibitorNon-inhibitor0.7801
CYP450 3A4 inhibitorNon-inhibitor0.8322
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9212
Ames testNon AMES toxic0.7448
CarcinogenicityNon-carcinogens0.9391
BiodegradationNot ready biodegradable1.0
Rat acute toxicity3.1511 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8366
hERG inhibition (predictor II)Non-inhibitor0.586
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-0a4i-9004200000-95c5673aa686eb387e74
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-014i-0000900000-41335c098b0866a02156
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-014i-0000900000-877684bddda5fa2f0b4c
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-014i-0000900000-9bd99c6a50b2b7abafcc
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-014i-0000900000-d1379b1aef0cd7ee0432
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-01bc-2001900000-a94610647fcf73e5717e
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-014i-0000900000-c8ddacd69887f73bbf8f
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-216.9121418
predicted
DarkChem Lite v0.1.0
[M-H]-217.7359418
predicted
DarkChem Lite v0.1.0
[M-H]-217.20308
predicted
DeepCCS 1.0 (2019)
[M+H]+213.6722418
predicted
DarkChem Lite v0.1.0
[M+H]+217.3069418
predicted
DarkChem Lite v0.1.0
[M+H]+219.0985
predicted
DeepCCS 1.0 (2019)
[M+Na]+214.6286418
predicted
DarkChem Lite v0.1.0
[M+Na]+217.4496418
predicted
DarkChem Lite v0.1.0
[M+Na]+224.87642
predicted
DeepCCS 1.0 (2019)

Targets

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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
G-protein coupled opioid receptor that functions as a receptor for endogenous alpha-neoendorphins and dynorphins, but has low affinity for beta-endorphins. Also functions as a receptor for various synthetic opioids and for the psychoactive diterpene salvinorin A. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling leads to the inhibition of adenylate cyclase activity. Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Plays a role in the perception of pain. Plays a role in mediating reduced physical activity upon treatment with synthetic opioids. Plays a role in the regulation of salivation in response to synthetic opioids. May play a role in arousal and regulation of autonomic and neuroendocrine functions
Specific Function
dynorphin receptor activity
Gene Name
OPRK1
Uniprot ID
P41145
Uniprot Name
Kappa-type opioid receptor
Molecular Weight
42644.665 Da
References
  1. Boothby LA, Doering PL: Buprenorphine for the treatment of opioid dependence. Am J Health Syst Pharm. 2007 Feb 1;64(3):266-72. [Article]
  2. Robinson SE: Buprenorphine-containing treatments: place in the management of opioid addiction. CNS Drugs. 2006;20(9):697-712. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Partial agonist
General Function
Receptor for endogenous opioids such as beta-endorphin and endomorphin (PubMed:10529478, PubMed:12589820, PubMed:7891175, PubMed:7905839, PubMed:7957926, PubMed:9689128). Receptor for natural and synthetic opioids including morphine, heroin, DAMGO, fentanyl, etorphine, buprenorphin and methadone (PubMed:10529478, PubMed:10836142, PubMed:12589820, PubMed:19300905, PubMed:7891175, PubMed:7905839, PubMed:7957926, PubMed:9689128). Also activated by enkephalin peptides, such as Met-enkephalin or Met-enkephalin-Arg-Phe, with higher affinity for Met-enkephalin-Arg-Phe (By similarity). Agonist binding to the receptor induces coupling to an inactive GDP-bound heterotrimeric G-protein complex and subsequent exchange of GDP for GTP in the G-protein alpha subunit leading to dissociation of the G-protein complex with the free GTP-bound G-protein alpha and the G-protein beta-gamma dimer activating downstream cellular effectors (PubMed:7905839). The agonist- and cell type-specific activity is predominantly coupled to pertussis toxin-sensitive G(i) and G(o) G alpha proteins, GNAI1, GNAI2, GNAI3 and GNAO1 isoforms Alpha-1 and Alpha-2, and to a lesser extent to pertussis toxin-insensitive G alpha proteins GNAZ and GNA15 (PubMed:12068084). They mediate an array of downstream cellular responses, including inhibition of adenylate cyclase activity and both N-type and L-type calcium channels, activation of inward rectifying potassium channels, mitogen-activated protein kinase (MAPK), phospholipase C (PLC), phosphoinositide/protein kinase (PKC), phosphoinositide 3-kinase (PI3K) and regulation of NF-kappa-B (By similarity). Also couples to adenylate cyclase stimulatory G alpha proteins (By similarity). The selective temporal coupling to G-proteins and subsequent signaling can be regulated by RGSZ proteins, such as RGS9, RGS17 and RGS4 (By similarity). Phosphorylation by members of the GPRK subfamily of Ser/Thr protein kinases and association with beta-arrestins is involved in short-term receptor desensitization (By similarity). Beta-arrestins associate with the GPRK-phosphorylated receptor and uncouple it from the G-protein thus terminating signal transduction (By similarity). The phosphorylated receptor is internalized through endocytosis via clathrin-coated pits which involves beta-arrestins (By similarity). The activation of the ERK pathway occurs either in a G-protein-dependent or a beta-arrestin-dependent manner and is regulated by agonist-specific receptor phosphorylation (By similarity). Acts as a class A G-protein coupled receptor (GPCR) which dissociates from beta-arrestin at or near the plasma membrane and undergoes rapid recycling (By similarity). Receptor down-regulation pathways are varying with the agonist and occur dependent or independent of G-protein coupling (By similarity). Endogenous ligands induce rapid desensitization, endocytosis and recycling (By similarity). Heterooligomerization with other GPCRs can modulate agonist binding, signaling and trafficking properties (By similarity)
Specific Function
beta-endorphin receptor activity
Gene Name
OPRM1
Uniprot ID
P35372
Uniprot Name
Mu-type opioid receptor
Molecular Weight
44778.855 Da
References
  1. Kishioka S, Paronis CA, Lewis JW, Woods JH: Buprenorphine and methoclocinnamox: agonist and antagonist effects on respiratory function in rhesus monkeys. Eur J Pharmacol. 2000 Mar 17;391(3):289-97. [Article]
  2. Zubieta J, Greenwald MK, Lombardi U, Woods JH, Kilbourn MR, Jewett DM, Koeppe RA, Schuster CR, Johanson CE: Buprenorphine-induced changes in mu-opioid receptor availability in male heroin-dependent volunteers: a preliminary study. Neuropsychopharmacology. 2000 Sep;23(3):326-34. [Article]
  3. Sanchez-Blazquez P, Gomez-Serranillos P, Garzon J: Agonists determine the pattern of G-protein activation in mu-opioid receptor-mediated supraspinal analgesia. Brain Res Bull. 2001 Jan 15;54(2):229-35. [Article]
  4. Mizoguchi H, Wu HE, Narita M, Hall FS, Sora I, Uhl GR, Nagase H, Tseng LF: Antagonistic property of buprenorphine for putative epsilon-opioid receptor-mediated G-protein activation by beta-endorphin in pons/medulla of the mu-opioid receptor knockout mouse. Neuroscience. 2002;115(3):715-21. [Article]
  5. Ide S, Minami M, Satoh M, Uhl GR, Sora I, Ikeda K: Buprenorphine antinociception is abolished, but naloxone-sensitive reward is retained, in mu-opioid receptor knockout mice. Neuropsychopharmacology. 2004 Sep;29(9):1656-63. [Article]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
General Function
G-protein coupled receptor that functions as a receptor for endogenous enkephalins and for a subset of other opioids. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling leads to the inhibition of adenylate cyclase activity. Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Plays a role in the perception of pain and in opiate-mediated analgesia. Plays a role in developing analgesic tolerance to morphine
Specific Function
G protein-coupled enkephalin receptor activity
Gene Name
OPRD1
Uniprot ID
P41143
Uniprot Name
Delta-type opioid receptor
Molecular Weight
40368.235 Da
References
  1. Induru RR, Davis MP: Buprenorphine for neuropathic pain--targeting hyperalgesia. Am J Hosp Palliat Care. 2009 Dec-2010 Jan;26(6):470-3. doi: 10.1177/1049909109341868. Epub 2009 Aug 7. [Article]
  2. Lester PA, Traynor JR: Comparison of the in vitro efficacy of mu, delta, kappa and ORL1 receptor agonists and non-selective opioid agonists in dog brain membranes. Brain Res. 2006 Feb 16;1073-1074:290-6. Epub 2006 Jan 27. [Article]
  3. Megarbane B, Marie N, Pirnay S, Borron SW, Gueye PN, Risede P, Monier C, Noble F, Baud FJ: Buprenorphine is protective against the depressive effects of norbuprenorphine on ventilation. Toxicol Appl Pharmacol. 2006 May 1;212(3):256-67. Epub 2005 Sep 16. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
G-protein coupled opioid receptor that functions as a receptor for the endogenous neuropeptide nociceptin. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Signaling via G proteins mediates inhibition of adenylate cyclase activity and calcium channel activity. Arrestins modulate signaling via G proteins and mediate the activation of alternative signaling pathways that lead to the activation of MAP kinases. Plays a role in modulating nociception and the perception of pain. Plays a role in the regulation of locomotor activity by the neuropeptide nociceptin
Specific Function
G protein-coupled receptor activity
Gene Name
OPRL1
Uniprot ID
P41146
Uniprot Name
Nociceptin receptor
Molecular Weight
40692.775 Da
References
  1. Bloms-Funke P, Gillen C, Schuettler AJ, Wnendt S: Agonistic effects of the opioid buprenorphine on the nociceptin/OFQ receptor. Peptides. 2000 Jul;21(7):1141-6. [Article]
  2. Lutfy K, Eitan S, Bryant CD, Yang YC, Saliminejad N, Walwyn W, Kieffer BL, Takeshima H, Carroll FI, Maidment NT, Evans CJ: Buprenorphine-induced antinociception is mediated by mu-opioid receptors and compromised by concomitant activation of opioid receptor-like receptors. J Neurosci. 2003 Nov 12;23(32):10331-7. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:19965576, PubMed:20702771, PubMed:21490593, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:21490593, PubMed:21576599, PubMed:2732228). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:12865317, PubMed:14559847). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:15373842, PubMed:15764715, PubMed:22773874, PubMed:2732228). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:15373842, PubMed:15764715, PubMed:2732228). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981)
Specific Function
1,8-cineole 2-exo-monooxygenase activity
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [Article]
  2. Kobayashi K, Yamamoto T, Chiba K, Tani M, Shimada N, Ishizaki T, Kuroiwa Y: Human buprenorphine N-dealkylation is catalyzed by cytochrome P450 3A4. Drug Metab Dispos. 1998 Aug;26(8):818-21. [Article]
  3. McCance-Katz EF, Sullivan LE, Nallani S: Drug interactions of clinical importance among the opioids, methadone and buprenorphine, and other frequently prescribed medications: a review. Am J Addict. 2010 Jan-Feb;19(1):4-16. doi: 10.1111/j.1521-0391.2009.00005.x. [Article]
  4. Zhang W, Ramamoorthy Y, Tyndale RF, Sellers EM: Interaction of buprenorphine and its metabolite norbuprenorphine with cytochromes p450 in vitro. Drug Metab Dispos. 2003 Jun;31(6):768-72. doi: 10.1124/dmd.31.6.768. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
A cytochrome P450 monooxygenase involved in the metabolism of steroid hormones and vitamins (PubMed:10681376, PubMed:11093772, PubMed:12865317, PubMed:2732228). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:10681376, PubMed:11093772, PubMed:12865317, PubMed:2732228). Exhibits high catalytic activity for the formation of catechol estrogens from 17beta-estradiol (E2) and estrone (E1), namely 2-hydroxy E1 and E2 (PubMed:12865317). Catalyzes 6beta-hydroxylation of the steroid hormones testosterone, progesterone, and androstenedione (PubMed:2732228). Catalyzes the oxidative conversion of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes all trans-retinoic acid (atRA) to 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Also involved in the oxidative metabolism of xenobiotics, including calcium channel blocking drug nifedipine and immunosuppressive drug cyclosporine (PubMed:2732228)
Specific Function
aromatase activity
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [Article]
  2. Coe MA, Lofwall MR, Walsh SL: Buprenorphine Pharmacology Review: Update on Transmucosal and Long-acting Formulations. J Addict Med. 2019 Mar/Apr;13(2):93-103. doi: 10.1097/ADM.0000000000000457. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids and steroids (PubMed:12865317, PubMed:15766564, PubMed:19965576, PubMed:21576599, PubMed:7574697, PubMed:9435160, PubMed:9866708). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:12865317, PubMed:15766564, PubMed:19965576, PubMed:21576599, PubMed:7574697, PubMed:9435160, PubMed:9866708). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:15766564, PubMed:19965576, PubMed:7574697, PubMed:9866708). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Exhibits low catalytic activity for the formation of catechol estrogens from 17beta-estradiol (E2) and estrone (E1), namely 2-hydroxy E1 and E2 (PubMed:12865317). Catalyzes bisallylic hydroxylation and hydroxylation with double-bond migration of polyunsaturated fatty acids (PUFA) (PubMed:9435160, PubMed:9866708). Also metabolizes plant monoterpenes such as limonene. Oxygenates (R)- and (S)-limonene to produce carveol and perillyl alcohol (PubMed:11950794). Contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan (PubMed:25994031)
Specific Function
(R)-limonene 6-monooxygenase activity
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [Article]
  2. Picard N, Cresteil T, Djebli N, Marquet P: In vitro metabolism study of buprenorphine: evidence for new metabolic pathways. Drug Metab Dispos. 2005 May;33(5):689-95. doi: 10.1124/dmd.105.003681. Epub 2005 Mar 2. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:11093772, PubMed:14559847, PubMed:15766564, PubMed:19965576, PubMed:7574697). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:11093772, PubMed:14559847, PubMed:15766564, PubMed:19965576, PubMed:7574697). Primarily catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) with a preference for the last double bond (PubMed:15766564, PubMed:19965576, PubMed:7574697). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes all trans-retinoic acid toward its 4-hydroxylated form (PubMed:11093772). Displays 16-alpha hydroxylase activity toward estrogen steroid hormones, 17beta-estradiol (E2) and estrone (E1) (PubMed:14559847). Plays a role in the oxidative metabolism of xenobiotics. It is the principal enzyme responsible for the metabolism of the anti-cancer drug paclitaxel (taxol) (PubMed:26427316)
Specific Function
arachidonic acid epoxygenase activity
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. Moody DE, Chang Y, Huang W, McCance-Katz EF: The in vivo response of novel buprenorphine metabolites, M1 and M3, to antiretroviral inducers and inhibitors of buprenorphine metabolism. Basic Clin Pharmacol Toxicol. 2009 Sep;105(3):211-5. doi: 10.1111/j.1742-7843.2009.00432.x. Epub 2009 Jun 4. [Article]
  2. Picard N, Cresteil T, Djebli N, Marquet P: In vitro metabolism study of buprenorphine: evidence for new metabolic pathways. Drug Metab Dispos. 2005 May;33(5):689-95. doi: 10.1124/dmd.105.003681. Epub 2005 Mar 2. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
A cytochrome P450 monooxygenase involved in the metabolism of steroid hormones and vitamins during embryogenesis (PubMed:11093772, PubMed:12865317, PubMed:14559847, PubMed:17178770, PubMed:9555064). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:11093772, PubMed:12865317, PubMed:14559847, PubMed:17178770, PubMed:9555064). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes 3beta-hydroxyandrost-5-en-17-one (dehydroepiandrosterone, DHEA), a precursor in the biosynthesis of androgen and estrogen steroid hormones (PubMed:17178770, PubMed:9555064). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1), particularly D-ring hydroxylated estrone at the C16-alpha position (PubMed:12865317, PubMed:14559847). Mainly hydroxylates all trans-retinoic acid (atRA) to 4-hydroxyretinoate and may play a role in atRA clearance during fetal development (PubMed:11093772). Also involved in the oxidative metabolism of xenobiotics including anticonvulsants (PubMed:9555064)
Specific Function
all-trans retinoic acid 18-hydroxylase activity
Gene Name
CYP3A7
Uniprot ID
P24462
Uniprot Name
Cytochrome P450 3A7
Molecular Weight
57469.95 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [Article]
  2. Picard N, Cresteil T, Djebli N, Marquet P: In vitro metabolism study of buprenorphine: evidence for new metabolic pathways. Drug Metab Dispos. 2005 May;33(5):689-95. doi: 10.1124/dmd.105.003681. Epub 2005 Mar 2. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
A cytochrome P450 monooxygenase involved in the metabolism of fatty acids, steroids and retinoids (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:19965576, PubMed:20972997). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 20-hydroxyeicosatetraenoic acid ethanolamide (20-HETE-EA) and 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:18698000, PubMed:21289075). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Catalyzes the oxidative transformations of all-trans retinol to all-trans retinal, a precursor for the active form all-trans-retinoic acid (PubMed:10681376). Also involved in the oxidative metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants
Specific Function
anandamide 11,12 epoxidase activity
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Umeda S, Harakawa N, Yamamoto M, Ueno K: Effect of nonspecific binding to microsomes and metabolic elimination of buprenorphine on the inhibition of cytochrome P4502D6. Biol Pharm Bull. 2005 Feb;28(2):212-6. [Article]
  2. Zhang W, Ramamoorthy Y, Tyndale RF, Sellers EM: Interaction of buprenorphine and its metabolite norbuprenorphine with cytochromes p450 in vitro. Drug Metab Dispos. 2003 Jun;31(6):768-72. doi: 10.1124/dmd.31.6.768. [Article]
  3. Umehara K, Shimokawa Y, Miyamoto G: Inhibition of human drug metabolizing cytochrome P450 by buprenorphine. Biol Pharm Bull. 2002 May;25(5):682-5. doi: 10.1248/bpb.25.682. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
A cytochrome P450 monooxygenase involved in retinoid metabolism. Hydroxylates all trans-retinoic acid (atRA) to 4-hydroxyretinoate and may modulate atRA signaling and clearance. Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase)
Specific Function
arachidonic acid epoxygenase activity
Gene Name
CYP2C18
Uniprot ID
P33260
Uniprot Name
Cytochrome P450 2C18
Molecular Weight
55710.075 Da
References
  1. Picard N, Cresteil T, Djebli N, Marquet P: In vitro metabolism study of buprenorphine: evidence for new metabolic pathways. Drug Metab Dispos. 2005 May;33(5):689-95. doi: 10.1124/dmd.105.003681. Epub 2005 Mar 2. [Article]
  2. Joseph D, Schobelock MJ, Riesenberg RR, Vince BD, Webster LR, Adeniji A, Elgadi M, Huang F: Effect of steady-state faldaprevir on the pharmacokinetics of steady-state methadone and buprenorphine-naloxone in subjects receiving stable addiction management therapy. Antimicrob Agents Chemother. 2015 Jan;59(1):498-504. doi: 10.1128/AAC.04046-14. Epub 2014 Nov 10. [Article]
  3. Kacinko SL, Jones HE, Johnson RE, Choo RE, Huestis MA: Correlations of maternal buprenorphine dose, buprenorphine, and metabolite concentrations in meconium with neonatal outcomes. Clin Pharmacol Ther. 2008 Nov;84(5):604-12. doi: 10.1038/clpt.2008.156. Epub 2008 Aug 13. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
A cytochrome P450 monooxygenase involved in the metabolism of polyunsaturated fatty acids (PUFA) (PubMed:18577768, PubMed:19965576, PubMed:20972997). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:18577768, PubMed:19965576, PubMed:20972997). Catalyzes the hydroxylation of carbon-hydrogen bonds. Hydroxylates PUFA specifically at the omega-1 position (PubMed:18577768). Catalyzes the epoxidation of double bonds of PUFA (PubMed:19965576, PubMed:20972997). Also metabolizes plant monoterpenes such as limonene. Oxygenates (R)- and (S)-limonene to produce carveol and perillyl alcohol (PubMed:11950794). Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine. Hydroxylates fenbendazole at the 4' position (PubMed:23959307)
Specific Function
(R)-limonene 6-monooxygenase activity
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55944.565 Da
References
  1. Umehara K, Shimokawa Y, Miyamoto G: Inhibition of human drug metabolizing cytochrome P450 by buprenorphine. Biol Pharm Bull. 2002 May;25(5):682-5. doi: 10.1248/bpb.25.682. [Article]
  2. Bomsien S, Skopp G: An in vitro approach to potential methadone metabolic-inhibition interactions. Eur J Clin Pharmacol. 2007 Sep;63(9):821-7. doi: 10.1007/s00228-007-0327-z. Epub 2007 Jun 28. [Article]
  3. Picard N, Cresteil T, Djebli N, Marquet P: In vitro metabolism study of buprenorphine: evidence for new metabolic pathways. Drug Metab Dispos. 2005 May;33(5):689-95. doi: 10.1124/dmd.105.003681. Epub 2005 Mar 2. [Article]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Translocates drugs and phospholipids across the membrane (PubMed:2897240, PubMed:35970996, PubMed:8898203, PubMed:9038218). Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins (PubMed:8898203). Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells (PubMed:2897240, PubMed:35970996, PubMed:9038218)
Specific Function
ABC-type xenobiotic transporter activity
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
ATP-dependent translocase ABCB1
Molecular Weight
141477.255 Da
References
  1. Tournier N, Chevillard L, Megarbane B, Pirnay S, Scherrmann JM, Decleves X: Interaction of drugs of abuse and maintenance treatments with human P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2). Int J Neuropsychopharmacol. 2010 Aug;13(7):905-15. doi: 10.1017/S1461145709990848. Epub 2009 Nov 4. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Broad substrate specificity ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes a wide variety of physiological compounds, dietary toxins and xenobiotics from cells (PubMed:11306452, PubMed:12958161, PubMed:19506252, PubMed:20705604, PubMed:28554189, PubMed:30405239, PubMed:31003562). Involved in porphyrin homeostasis, mediating the export of protoporphyrin IX (PPIX) from both mitochondria to cytosol and cytosol to extracellular space, it also functions in the cellular export of heme (PubMed:20705604, PubMed:23189181). Also mediates the efflux of sphingosine-1-P from cells (PubMed:20110355). Acts as a urate exporter functioning in both renal and extrarenal urate excretion (PubMed:19506252, PubMed:20368174, PubMed:22132962, PubMed:31003562, PubMed:36749388). In kidney, it also functions as a physiological exporter of the uremic toxin indoxyl sulfate (By similarity). Also involved in the excretion of steroids like estrone 3-sulfate/E1S, 3beta-sulfooxy-androst-5-en-17-one/DHEAS, and other sulfate conjugates (PubMed:12682043, PubMed:28554189, PubMed:30405239). Mediates the secretion of the riboflavin and biotin vitamins into milk (By similarity). Extrudes pheophorbide a, a phototoxic porphyrin catabolite of chlorophyll, reducing its bioavailability (By similarity). Plays an important role in the exclusion of xenobiotics from the brain (Probable). It confers to cells a resistance to multiple drugs and other xenobiotics including mitoxantrone, pheophorbide, camptothecin, methotrexate, azidothymidine, and the anthracyclines daunorubicin and doxorubicin, through the control of their efflux (PubMed:11306452, PubMed:12477054, PubMed:15670731, PubMed:18056989, PubMed:31254042). In placenta, it limits the penetration of drugs from the maternal plasma into the fetus (By similarity). May play a role in early stem cell self-renewal by blocking differentiation (By similarity)
Specific Function
ABC-type xenobiotic transporter activity
Gene Name
ABCG2
Uniprot ID
Q9UNQ0
Uniprot Name
Broad substrate specificity ATP-binding cassette transporter ABCG2
Molecular Weight
72313.47 Da
References
  1. Tournier N, Chevillard L, Megarbane B, Pirnay S, Scherrmann JM, Decleves X: Interaction of drugs of abuse and maintenance treatments with human P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2). Int J Neuropsychopharmacol. 2010 Aug;13(7):905-15. doi: 10.1017/S1461145709990848. Epub 2009 Nov 4. [Article]

Drug created at June 13, 2005 13:24 / Updated at November 03, 2024 19:35