Naloxone

Identification

Summary

Naloxone is an opioid receptor antagonist used to rapidly reverse an opioid overdose. Also included in some drug formulations as an abuse deterrent to prevent injection.

Brand Names
Kloxxado, Narcan, Rextovy, Suboxone, Targin, Targiniq, Zimhi, Zubsolv
Generic Name
Naloxone
DrugBank Accession Number
DB01183
Background

Naloxone is an opioid antagonist medication used to block or reverse the effects of opioid drugs, particularly within the setting of drug overdoses which are rapidly becoming a leading cause of death worldwide.3 More specifically, naloxone has a high affinity for μ-opioid receptors, where it acts as an inverse agonist, causing the rapid removal of any other drugs bound to these receptors.3 When taken in large quantities, opioid medications such as morphine, hydromorphone, methadone, heroin, or fentanyl are capable of causing life-threatening symptoms such as respiratory depression, reduced heart rate, slurred speech, drowsiness, and constricted pupils.3,13 If untreated, this can progress to vomiting, absent pulse and breathing, loss of consciousness, and even death.13 Naloxone is indicated for the rapid reversal of these symptoms of central nervous system depression in opioid overdose.2 It's important to note that naloxone only works on opioid receptors within the body, and is therefore not capable of reversing the effects of non-opioid medications such as stimulants like methamphetamine or cocaine, or benzodiazepines like lorazepam or diazepam.

Also known as the brand name product Narcan, naloxone is currently available by intramuscular (IM) or subcutaneous (SubQ) injection, nasal spray, or intravenous (IV) infusion.14,16 Naloxone IM injections are commonly available in the form of "kits", which is ideal for making overdose treatment accessible and readily available for administration by minimally trained individuals within the community.15 Kits commonly include the supplies necessary to treat an overdose in a non-medical setting such as alcohol swabs, syringes, a rescue breathing mask, and instructions for use. Frequently also carried by medical and emergency personnel and at events known to be associated with heavy drug use like music festivals, naloxone kits are considered a key component of harm reduction strategies. There are over-the-counter nasal sprays available.

When injected intramuscularly (IM), naloxone acts within three to five minutes. Administration of naloxone is associated with very few side effects. Notably, if injected into a person not currently using opioid medications, there would be no noticeable effects at all. However, for individuals using opioid medications or experiencing an overdose, IM injection of naloxone rapidly reverses opioid effects and can cause the injected individual to immediately experience withdrawal symptoms.2 Common symptoms of opioid withdrawal include nausea, vomiting, sweating, runny nose, aches, and diarrhea.2 Although certainly physically uncomfortable, opioid withdrawal symptoms are not life-threatening; administration of naloxone is, therefore, appropriate for any person appearing to have any symptoms of an opioid overdose. Due to its short duration of action, persons injected with naloxone should be monitored for responsiveness and potentially injected a second time or taken to the hospital.2

Naloxone is also available within the combination product Suboxone with the opioid medication buprenorphine.11,12 Suboxone is used for the maintenance treatment of opioid dependence and addiction.11,12 When taken orally, naloxone has no pharmacological effect and does not reduce the effectiveness of the opioid effect of buprenorphine.11,12 The primary purpose of including naloxone within Suboxone is to act as a deterrent to injection, as injected naloxone would rapidly reverse the effects of buprenorphine.11,12

Naloxone was granted FDA approval on 13 April 1971.10

Type
Small Molecule
Groups
Approved, Vet approved
Structure
Weight
Average: 327.3743
Monoisotopic: 327.147058165
Chemical Formula
C19H21NO4
Synonyms
  • (−)-naloxone
  • 1-N-Allyl-14-hydroxynordihydromorphinone
  • 17-allyl-3,14-dihydroxy-4,5α-epoxymorphinan-6-one
  • Nalossone
  • Naloxona
  • Naloxone
  • Naloxonum
External IDs
  • EN 1530 Base

Pharmacology

Indication

Naloxone nasal sprays are indicated for the reversal of an opioid overdose or suspected opioid overdose: it is intended for immediate administration as emergency therapy in settings where opioids may be present.7,20 Intramuscular, intravenous, and subcutaneous injections are indicated for complete or partial reversal of opioid depression, diagnosis of known or suspected opioid overdose, and as an adjunct therapy in the treatment of septic shock.16

Sublingual tablets and films are formulated with buprenorphine for the treatment of opioid dependence.11,12 Naloxone is also formulated with pentazocine as an oral tablet for severe pain.17

Intramuscular or subcutaneous naloxone autoinjectors are used for the emergency treatment of people 12 years of age and older where the use of high-potency opioids such as fentanyl analogues as a chemical weapon, is suspected.18,19

Naloxone has been used off-label for the treatment of neuraxial opioid-induced pruritus.5

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Used in combination to treatOpioid dependenceCombination Product in combination with: Buprenorphine (DB00921)••••••••••••••••• ••••••
Reversal ofOpioid overdose••• •••
Reversal ofOpioid overdose•••••••••••••••••••••
Reversal ofOpioid overdose•••••••• •••
Diagnostic agentOpioid overdose•••••••••••••••••••••
Associated Therapies
Contraindications & Blackbox Warnings
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Pharmacodynamics

Naloxone is an opioid receptor antagonist indicated in the reversal of opioid overdoses.7 Naloxone has a shorter duration of action than opioids and multiple doses may be required.3,7 The therapeutic window of naloxone is wide, as it has no effect if a patient has not taken opioids.4,7 Patients treated with naloxone may experience opioid withdrawal and a person administering naloxone should be aware that reversal of opioid overdoses may not resolve all the symptoms a patient is experiencing if other drugs are involved.7

Mechanism of action

Naloxone is a competitive inhibitor of the µ-opioid receptor.7,12 Naloxone antagonizes the action of opioids, reversing their effects.7 If a patient has not taken opioids, naloxone does not have a significant effect on patients.13

TargetActionsOrganism
AMu-type opioid receptor
antagonist
Humans
ADelta-type opioid receptor
antagonist
Humans
AKappa-type opioid receptor
antagonist
Humans
NCyclic AMP-responsive element-binding protein 1
other/unknown
Humans
NEstrogen receptor
antagonist
other/unknown
Humans
UToll-like receptor 4
inhibitor
Humans
ULiver carboxylesterase 1
binder
Humans
Absorption

An intranasal dose of naloxone is 42-47% bioavailable.7 An 8 mg dose of nasal naloxone reaches a Cmax of 12.3-12.8 ng/mL, with a Tmax of 0.25 hours, and an AUC of 16.7-19.0 h*ng/mL.7 A 0.4 mg intramuscular dose reaches a Cmax of 0.876-0.910 ng/mL, with a Tmax of 0.25 hours, and an AUC of 1.94-1.95 h*ng/mL.7 A 2 mg intravenous dose reaches a Cmax of 26.2 ng/mL with an AUC of 12.8 h*ng/mL.7

Volume of distribution

The volume of distribution of naloxone is 200 L.3 Naloxone distributes into tissues rapidly.7 It can also cross the placenta and blood-brain barrier.7

Protein binding

Naloxone is approximately 45% bound to albumin, but there is significant binding to other proteins.7,12

Metabolism

Naloxone primarily undergoes glucuronidation to form naloxone-3-glucuronide.7 Naloxone is also N-dealkylated to noroxymorphone or undergoes 6-keto reduction to naloxol.1

Hover over products below to view reaction partners

Route of elimination

After oral or intravenous administration, naloxone is 25-40% eliminated in the urine within 6 hours, 50% in 24 hours, and 60-70% in 72 hours.7 The metabolites naloxone-3-glucuronide, noroxymorphone, and naloxol are all detected in the urine.1,7

Half-life

The mean half life of naloxone hydrochloride is 1.8-2.7 hours intranasally, 1.4 hours intramuscularly, and 1.2 hours intravenously.8 In neonates, the mean half life is 3.1 ± 0.5 hours.8

Clearance

The clearance of naloxone is 2500 L/day.3

Adverse Effects
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Toxicity

If a patient has not taken opioids, naloxone does not have a significant effect on patients.4,13

The oral LD50 in mice and rats is >1 g/kg.8 The intraperitoneal LD50 is 80 mg/kg in mice and 239 mg/kg in rats.8 The subcutaneous LD50 is 286 mg/kg in mice and 500 mg/kg in rats.8

Pathways
PathwayCategory
Naloxone 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
AbacavirAbacavir may decrease the excretion rate of Naloxone which could result in a higher serum level.
AceclofenacAceclofenac may decrease the excretion rate of Naloxone which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Naloxone which could result in a higher serum level.
AcetaminophenAcetaminophen may decrease the excretion rate of Naloxone which could result in a higher serum level.
AcetazolamideAcetazolamide may increase the excretion rate of Naloxone which could result in a lower serum level and potentially a reduction in efficacy.
Food Interactions
  • Take separate from meals. When formulated as a buccal film or sublingual form, avoid eating or drinking until the film has completely dissolved.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Naloxone hydrochlorideF850569PQR357-08-4RGPDIGOSVORSAK-STHHAXOLSA-N
Naloxone hydrochloride dihydrate5Q187997EE51481-60-8TXMZWEASFRBVKY-IOQDSZRYSA-N
Product Images
International/Other Brands
Kloxxado (Hikma Pharmaceuticals PLC) / Narcanti / Narcon
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
EvzioInjection, solution0.4 mg/1Intramuscular; SubcutaneousKaleo, Inc2014-04-032018-05-31US flag
EvzioInjection, solution2 mg/0.4mLIntramuscular; Subcutaneouskaleo, Inc.2016-10-192021-09-30US flag
EVZIO(R) NALOXONE HClInjection, solution2 mg/0.4mLIntramuscular; SubcutaneousHF Acquisition Co LLC, DBA HealthFirst2020-01-11Not applicableUS flag
Injectable Naloxone HydrochlorideSolution1 mg / mLIntramuscular; Intravenous; SubcutaneousOmega Laboratories LimitedNot applicableNot applicableCanada flag
Injectable Naloxone HydrochlorideSolution0.4 mg / mLIntramuscular; Intravenous; SubcutaneousOmega Laboratories Limited2016-08-05Not applicableCanada flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Naloxone HciInjection, solution0.4 mg/1mLIntramuscular; Intravenous; SubcutaneousHf Acquisition Co. Llc, Dba Health First2018-08-18Not applicableUS flag
Naloxone HClInjection0.4 mg/1mLIntramuscular; Intravenous; SubcutaneousRenaissance Ssa, Llc2019-12-28Not applicableUS flag
NALOXONE HClSpray4 mg/0.1mLNasalHF Acquisition Co LLC, DBA HealthFirst2023-04-10Not applicableUS flag
Naloxone HClSpray4 mg/0.1mLNasalAdvanced Rx Pharmacy of Tennessee, LLC2023-02-082024-12-31US flag
Naloxone HydrochlorideInjection, solution0.4 mg/1mLIntramuscular; Intravenous; SubcutaneousA-S Medication Solutions2017-02-28Not applicableUS flag
Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Naloxone HydrochlorideSpray4 mg/0.1mLNasalPadagis Israel Pharmaceuticals Ltd2023-07-30Not applicableUS flag
Naloxone HydrochlorideSpray4 mg/0.1mLNasalHF Acquisition Co LLC, DBA HealthFirst2023-07-30Not applicableUS flag
Naloxone HydrochlorideSpray4 mg/0.1mLNasalA-S Medication Solutions2023-07-30Not applicableUS flag
Naloxone HydrochlorideSpray4 mg/0.1mLNasalWALGREEN CO.2024-04-24Not applicableUS flag
Naloxone HydrochlorideSpray, metered4 mg/0.1mLNasalTeva Pharmaceuticals, Inc.2024-09-23Not applicableUS flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
APOKLISINaloxone hydrochloride (5 MG) + Oxycodone hydrochloride (10 MG)Tablet, extended releaseOralNeopharmed Gentili S.P.A.2020-10-132022-06-24Italy flag
APOKLISINaloxone hydrochloride (5 MG) + Oxycodone hydrochloride (10 MG)Tablet, extended releaseOralNeopharmed Gentili S.P.A.2020-05-282024-05-06Italy flag
APOKLISINaloxone hydrochloride (5 MG) + Oxycodone hydrochloride (10 MG)Tablet, extended releaseOralNeopharmed Gentili S.P.A.2020-05-282024-05-06Italy flag
APOKLISINaloxone hydrochloride (2.5 MG) + Oxycodone hydrochloride (5 MG)Tablet, extended releaseOralNeopharmed Gentili S.P.A.2020-05-282024-05-06Italy flag
APOKLISINaloxone hydrochloride (2.5 MG) + Oxycodone hydrochloride (5 MG)Tablet, extended releaseOralNeopharmed Gentili S.P.A.2020-05-282024-05-06Italy flag

Categories

ATC Codes
A06AH04 — NaloxoneN02AA53 — Hydromorphone and naloxoneN02AD51 — Pentazocine and naloxoneV03AB15 — NaloxoneN02AA55 — Oxycodone and naloxoneN02AX51 — Tilidine and naloxone
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
Isoquinolones and derivatives / Tetralins / Coumarans / 1-hydroxy-2-unsubstituted benzenoids / Alkyl aryl ethers / Aralkylamines / Piperidines / Tertiary alcohols / Trialkylamines / 1,2-aminoalcohols
show 7 more
Substituents
1,2-aminoalcohol / 1-hydroxy-2-unsubstituted benzenoid / Alcohol / Alkyl aryl ether / Amine / Aralkylamine / Aromatic heteropolycyclic compound / Azacycle / Carbonyl group / Coumaran
show 19 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
morphinane alkaloid, organic heteropentacyclic compound (CHEBI:7459)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
36B82AMQ7N
CAS number
465-65-6
InChI Key
UZHSEJADLWPNLE-GRGSLBFTSA-N
InChI
InChI=1S/C19H21NO4/c1-2-8-20-9-7-18-15-11-3-4-12(21)16(15)24-17(18)13(22)5-6-19(18,23)14(20)10-11/h2-4,14,17,21,23H,1,5-10H2/t14-,17+,18+,19-/m1/s1
IUPAC Name
(1S,5R,13R,17S)-10,17-dihydroxy-4-(prop-2-en-1-yl)-12-oxa-4-azapentacyclo[9.6.1.0^{1,13}.0^{5,17}.0^{7,18}]octadeca-7(18),8,10-trien-14-one
SMILES
OC1=CC=C2C[C@H]3N(CC=C)CC[C@@]45[C@@H](OC1=C24)C(=O)CC[C@@]35O

References

Synthesis Reference

Bianca Brogmann, Silke Muhlau, Christof Spitzley, "Pharmaceutical preparation containing oxycodone and naloxone." U.S. Patent US20050245556, issued November 03, 2005.

US20050245556
General References
  1. Weinstein SH, Pfeffer M, Schor JM, Indindoli L, Mintz M: Metabolites of naloxone in human urine. J Pharm Sci. 1971 Oct;60(10):1567-8. doi: 10.1002/jps.2600601030. [Article]
  2. Jordan MR, Morrisonponce D: Naloxone . [Article]
  3. Rzasa Lynn R, Galinkin JL: Naloxone dosage for opioid reversal: current evidence and clinical implications. Ther Adv Drug Saf. 2018 Jan;9(1):63-88. doi: 10.1177/2042098617744161. Epub 2017 Dec 13. [Article]
  4. Papathanasiou T, Springborg AD, Kongstad KT, Staerk D, Moller K, Taylor BK, Lund TM, Werner MU: High-dose naloxone, an experimental tool uncovering latent sensitisation: pharmacokinetics in humans. Br J Anaesth. 2019 Aug;123(2):e204-e214. doi: 10.1016/j.bja.2018.12.007. Epub 2019 Jan 18. [Article]
  5. Kumar K, Singh SI: Neuraxial opioid-induced pruritus: An update. J Anaesthesiol Clin Pharmacol. 2013 Jul;29(3):303-7. doi: 10.4103/0970-9185.117045. [Article]
  6. Link [Link]
  7. FDA Approved Drug Products: Kloxxado (Naloxone) Nasal Spray [Link]
  8. Caymen Chemical: Naloxone MSDS [Link]
  9. International Pharmacopoeia: Naloxone Hydrochloride [Link]
  10. FDA Approved Drug Products: Narcan (Naloxone) Injection (Discontinued) [Link]
  11. FDA Approved Drug Products: Suboxone (Buprenorphine, Naloxone) Sublingual, Buccal Film [Link]
  12. FDA Approved Drug Products: Zubsolv (Buprenorphine, Naloxone) Sublingual Tablet [Link]
  13. British Columbia CDC: Administration of Naloxone [Link]
  14. FDA Approved Drug Products: Narcan (Naloxone) Nasal Spray [Link]
  15. DailyMed: Lifems (Naloxone Hydrochloride) Kit [Link]
  16. Dailymed: Naloxone Hydrochloride Subcutaneous, Intramuscular, Intravenous Injection [Link]
  17. DailyMed: Naloxone and Pentazocine Oral Tablet [Link]
  18. FDA Approved Drug Products: Naloxone Hydrochloride Injection Auto-Injector (referred throughout as NALOXONE AUTO-INJECTOR) for intramuscular or subcutaneous use [Link]
  19. Kaléo News: FDA Approves Kaléo’s Naloxone Auto-Injector 10 mg for the Treatment of Known or Potential Exposure to Ultra-Potent Weaponized Opioids [Link]
  20. FDA Approved Drug Products: Naloxone Hydrochloride Nasal Spray [Link]
  21. FDA Approved Drug Products: NARCAN® (naloxone hydrochloride) Nasal Spray [Link]
Human Metabolome Database
HMDB0015314
KEGG Drug
D08249
KEGG Compound
C07252
PubChem Compound
5284596
PubChem Substance
46508816
ChemSpider
4447644
BindingDB
54795
RxNav
7242
ChEBI
7459
ChEMBL
CHEMBL80
ZINC
ZINC000000389747
Therapeutic Targets Database
DAP000097
PharmGKB
PA450586
Guide to Pharmacology
GtP Drug Page
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Naloxone
MSDS
Download (74 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 AvailableActive Not RecruitingNot AvailableOpioid Abuse1somestatusstop reasonjust information to hide
Not AvailableActive Not RecruitingHealth Services ResearchAddiction / Hepatitis / Human Immunodeficiency Virus Infection(HIV)/Acquired Immunodeficiency Syndrome (AIDS) / Opioid Dependence / Tuberculosis (TB)1somestatusstop reasonjust information to hide
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 AvailableCancer Pain / Neoplasm1somestatusstop reasonjust information to hide

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Amphastar Pharmaceuticals
  • A-S Medication Solutions LLC
  • Bristol-Myers Squibb Co.
  • Bryant Ranch Prepack
  • Cardinal Health
  • Dispensing Solutions
  • Diversified Healthcare Services Inc.
  • Endo Pharmaceuticals Inc.
  • General Injectables and Vaccines Inc.
  • Hospira Inc.
  • Lake Erie Medical and Surgical Supply
  • Letco Medical Inc.
  • Mallinckrodt Inc.
  • Mckesson Corp.
  • Nucare Pharmaceuticals Inc.
  • Physicians Total Care Inc.
  • Reckitt Benckiser Inc.
  • Southwood Pharmaceuticals
  • Stat Rx Usa
Dosage Forms
FormRouteStrength
Tablet, extended releaseOral20 MG
FilmBuccal
FilmBuccal; Sublingual
Film, solubleBuccal; Sublingual
Injection, solution0.4 mg/1ml
Injection, solutionIntramuscular; Subcutaneous0.4 mg/1
Injection, solutionIntramuscular; Subcutaneous2 mg/0.4mL
SprayNasal8 mg/0.1mL
SolutionParenteral0.040 mg
Injection; kitParenteral; Topical
InjectionIntramuscular; Intravenous
InjectionIntramuscular; Intravenous; Subcutaneous0.4 mg/ml
Injection0.4 mg/ml
SolutionParenteral0.4 mg
SolutionIntramuscular; Intravenous; Subcutaneous0.4 mg
SprayNasal10 mg/0.1mL
SprayNasal3.6 MG
Injection, solutionParenteral0.4 MG/ML
Injection, solution0.4 MG/ML
Injection, solutionIntramuscular; Intravenous; Subcutaneous0.04 MG/2ML
Injection, solution
Injection, solution0.04 MG/2ML
LiquidIntramuscular; Intravenous; Subcutaneous0.4 mg / mL
LiquidIntramuscular; Intravenous; Subcutaneous1 mg / mL
InhalantNasal4 mg/0.1mL
Injection0.4 mg/2ml
InjectionIntramuscular; Intravenous; Subcutaneous0.4 mg/1mL
InjectionIntramuscular; Intravenous; Subcutaneous1 mg/1mL
InjectionParenteral0.4 mg/1mL
InjectionParenteral1 mg/1mL
InjectionParenteral4 mg/1mL
Injection, solutionIntramuscular; Intravenous; Subcutaneous.4 mg/1mL
Injection, solutionIntramuscular; Intravenous; Subcutaneous0.02 mg/1mL
Injection, solutionIntramuscular; Intravenous; Subcutaneous0.4 mg/1mL
Injection, solutionIntramuscular; Intravenous; Subcutaneous1 mg/1mL
Spray, meteredNasal4 mg/0.1mL
Injection0.44 mg/2ml
PowderNot applicable1 kg/1kg
SolutionIntramuscular; Subcutaneous0.4 mg / mL
SolutionIntramuscular; Intravenous; Subcutaneous4 mg / 10 mL
Injection, solutionIntramuscular; Subcutaneous10 mg/0.4mL
InjectionParenteral0.4 mg/ml
InjectionIntravenous0.02 mg/1mL
InjectionIntravenous0.4 mg/1mL
InjectionIntravenous1 mg/1mL
SprayNasal2 mg/0.1mL
SprayNasal4 mg/0.1mL
LiquidIntramuscular; Intravenous; Subcutaneous0.02 mg / mL
SolutionIntramuscular; Intravenous; Subcutaneous0.4 mg / mL
Spray, meteredNasal2 mg / 0.1 mL
Spray, meteredNasal4 mg / 0.1 mL
Solution0.4 mg/1ml
SprayNasal1.8 MG
Tablet, extended releaseOral
TabletOral
SolutionIntramuscular0.400 mg
SprayNasal4 mg/0.25mL
SprayNasal3 mg/0.1mL
SolutionIntramuscular; Intravenous; Subcutaneous1 mg / mL
Film, solubleSublingual
TabletOral; Sublingual
TabletSublingual
Tablet, orally disintegratingSublingual2.16 MG
Tablet, orally disintegratingSublingual8.64 MG
FilmSublingual
Tablet, film coated, extended releaseOral5 mg
Tablet, film coated, extended releaseOral10 mg
Tablet, film coated, extended releaseOral20 mg
Tablet, film coated, extended releaseOral2.5 mg
Tablet, film coated, extended releaseOral
SolutionOral
SprayNasal
SprayNasal1.26 MG
Injection, solutionIntramuscular; Subcutaneous5 mg/0.5mL
Tablet, orally disintegratingSublingual
Prices
Unit descriptionCostUnit
Naloxone hcl powder70.9USD g
Naloxone 0.4 mg/ml vial7.07USD ml
Naloxone 0.4 mg/ml ampul4.78USD ml
Narcan 0.4 mg/ml ampul4.58USD ml
Naloxone 0.02 mg/ml vial0.84USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
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US8940330No2015-01-272032-09-18US flag
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Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)177 °CInternational Pharmacopoeia
water solubilitySolubleFDA Label
logP2.09HANSCH,C ET AL. (1995)
Predicted Properties
PropertyValueSource
Water Solubility5.64 mg/mLALOGPS
logP1.47ALOGPS
logP1.62Chemaxon
logS-1.8ALOGPS
pKa (Strongest Acidic)10.07Chemaxon
pKa (Strongest Basic)7.84Chemaxon
Physiological Charge1Chemaxon
Hydrogen Acceptor Count5Chemaxon
Hydrogen Donor Count2Chemaxon
Polar Surface Area70 Å2Chemaxon
Rotatable Bond Count2Chemaxon
Refractivity88.72 m3·mol-1Chemaxon
Polarizability33.83 Å3Chemaxon
Number of Rings5Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9729
Blood Brain Barrier+0.9787
Caco-2 permeable+0.8867
P-glycoprotein substrateSubstrate0.8788
P-glycoprotein inhibitor INon-inhibitor0.7922
P-glycoprotein inhibitor IINon-inhibitor0.8382
Renal organic cation transporterInhibitor0.5
CYP450 2C9 substrateNon-substrate0.8522
CYP450 2D6 substrateSubstrate0.5296
CYP450 3A4 substrateSubstrate0.6107
CYP450 1A2 substrateNon-inhibitor0.9046
CYP450 2C9 inhibitorNon-inhibitor0.9303
CYP450 2D6 inhibitorNon-inhibitor0.7886
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.9153
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9523
Ames testNon AMES toxic0.7182
CarcinogenicityNon-carcinogens0.9583
BiodegradationNot ready biodegradable0.9968
Rat acute toxicity2.7231 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7798
hERG inhibition (predictor II)Non-inhibitor0.8641
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-MSsplash10-0a6r-9042000000-3da4b2172456d62748f0
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSsplash10-00di-0900000000-6b7de93b51a79132630f
MS/MS Spectrum - , positiveLC-MS/MSsplash10-004i-0139000000-e70921e0765c3389ce85
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-004i-0009000000-c13fe4975c4024fda4df
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-004i-0009000000-82b88423f7e0348864a8
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-03di-0049000000-acbab4943d3b020228f2
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-004i-0009000000-55fe12ef8698501c5ab3
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-056r-0059000000-e1e17b878e91b2ba28b9
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-024i-1093000000-681d2c39457d1043efbc
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]-180.7506744
predicted
DarkChem Lite v0.1.0
[M-H]-181.48648
predicted
DeepCCS 1.0 (2019)
[M+H]+180.8025744
predicted
DarkChem Lite v0.1.0
[M+H]+183.87685
predicted
DeepCCS 1.0 (2019)
[M+Na]+180.7681744
predicted
DarkChem Lite v0.1.0
[M+Na]+191.71365
predicted
DeepCCS 1.0 (2019)

Targets

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Details
1. Mu-type opioid receptor
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
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. Narita M, Suzuki M, Mizoguchi H, Narita M, Yajima Y, Sakurada S, Tseng LF, Suzuki T: Up-regulation of mu-opioid receptor-mediated G-protein activation in protein kinase Cgamma knockout mice following repeated naloxone treatment. Neurosci Lett. 2003 Feb 27;338(2):103-6. [Article]
  2. Freye E, Latasch L, Von Bredow G, Neruda B: [The opioid tramadol demonstrates excitatory properties of non-opioid character--a preclinical study using alfentanil as a comparison]. Schmerz. 1998 Feb 28;12(1):19-24. [Article]
  3. Neal CR Jr, Owens CE, Taylor LP, Hoversten MT, Akil H, Watson SJ Jr: Binding and GTPgammaS autoradiographic analysis of preproorphanin precursor peptide products at the ORL1 and opioid receptors. J Chem Neuroanat. 2003 Jul;25(4):233-47. [Article]
  4. Spetea M, Toth F, Schutz J, Otvos F, Toth G, Benyhe S, Borsodi A, Schmidhammer H: Binding characteristics of [3H]14-methoxymetopon, a high affinity mu-opioid receptor agonist. Eur J Neurosci. 2003 Jul;18(2):290-5. [Article]
  5. Marek GJ: Behavioral evidence for mu-opioid and 5-HT2A receptor interactions. Eur J Pharmacol. 2003 Aug 1;474(1):77-83. [Article]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
  7. Helm S, Trescot AM, Colson J, Sehgal N, Silverman S: Opioid antagonists, partial agonists, and agonists/antagonists: the role of office-based detoxification. Pain Physician. 2008 Mar-Apr;11(2):225-35. [Article]
  8. Goodman AJ, Le Bourdonnec B, Dolle RE: Mu opioid receptor antagonists: recent developments. ChemMedChem. 2007 Nov;2(11):1552-70. [Article]
  9. van Dorp E, Yassen A, Dahan A: Naloxone treatment in opioid addiction: the risks and benefits. Expert Opin Drug Saf. 2007 Mar;6(2):125-32. [Article]
  10. Nazzaro C, Rizzi A, Salvadori S, Guerrini R, Regoli D, Zeilhofer HU, Calo G: UFP-101 antagonizes the spinal antinociceptive effects of nociceptin/orphanin FQ: behavioral and electrophysiological studies in mice. Peptides. 2007 Mar;28(3):663-9. doi: 10.1016/j.peptides.2006.11.004. Epub 2006 Dec 11. [Article]
  11. Economidou D, Fedeli A, Fardon RM, Weiss F, Massi M, Ciccocioppo R: Effect of novel nociceptin/orphanin FQ-NOP receptor ligands on ethanol drinking in alcohol-preferring msP rats. Peptides. 2006 Dec;27(12):3299-306. doi: 10.1016/j.peptides.2006.09.007. [Article]
  12. Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
  13. FDA Approved Drug Products: Zubsolv (Buprenorphine, Naloxone) Sublingual Tablet [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
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. Moncada A, Cendan CM, Baeyens JM, Del Pozo E: Effects of serine/threonine protein phosphatase inhibitors on morphine-induced antinociception in the tail flick test in mice. Eur J Pharmacol. 2003 Mar 28;465(1-2):53-60. [Article]
  2. Kakinohana M, Marsala M, Carter C, Davison JK, Yaksh TL: Neuraxial morphine may trigger transient motor dysfunction after a noninjurious interval of spinal cord ischemia: a clinical and experimental study. Anesthesiology. 2003 Apr;98(4):862-70. [Article]
  3. Breljak D, Boranic M, Horvat S: Oligopeptide fragments of the enkephalin molecule interfere with hematopoietic cell colony formation. Int J Immunopathol Pharmacol. 2000 Jan-Apr;13(1):13-19. [Article]
  4. Chudapongse N, Kim SY, Kramer RE, Ho IK: Nonspecific effects of the selective kappa-opioid receptor agonist U-50,488H on dopamine uptake and release in PC12 cells. J Pharmacol Sci. 2003 Nov;93(3):372-5. [Article]
  5. Osman AM, Gomma M, Saad AH: A possible role for an enkephalinergic system in the internal defense mechanism of Biomphalaria alexandrina exposed to Schistosoma mansoni. J Egypt Soc Parasitol. 2003 Dec;33(3):841-61. [Article]
  6. Helm S, Trescot AM, Colson J, Sehgal N, Silverman S: Opioid antagonists, partial agonists, and agonists/antagonists: the role of office-based detoxification. Pain Physician. 2008 Mar-Apr;11(2):225-35. [Article]
  7. van Dorp E, Yassen A, Dahan A: Naloxone treatment in opioid addiction: the risks and benefits. Expert Opin Drug Saf. 2007 Mar;6(2):125-32. [Article]
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. Peng X, Neumeyer JL: Kappa receptor bivalent ligands. Curr Top Med Chem. 2007;7(4):363-73. [Article]
  2. van Dorp E, Yassen A, Dahan A: Naloxone treatment in opioid addiction: the risks and benefits. Expert Opin Drug Saf. 2007 Mar;6(2):125-32. [Article]
  3. Helm S, Trescot AM, Colson J, Sehgal N, Silverman S: Opioid antagonists, partial agonists, and agonists/antagonists: the role of office-based detoxification. Pain Physician. 2008 Mar-Apr;11(2):225-35. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Other/unknown
General Function
Phosphorylation-dependent transcription factor that stimulates transcription upon binding to the DNA cAMP response element (CRE), a sequence present in many viral and cellular promoters (By similarity). Transcription activation is enhanced by the TORC coactivators which act independently of Ser-119 phosphorylation (PubMed:14536081). Involved in different cellular processes including the synchronization of circadian rhythmicity and the differentiation of adipose cells (By similarity). Regulates the expression of apoptotic and inflammatory response factors in cardiomyocytes in response to ERFE-mediated activation of AKT signaling (By similarity)
Specific Function
cAMP response element binding
Gene Name
CREB1
Uniprot ID
P16220
Uniprot Name
Cyclic AMP-responsive element-binding protein 1
Molecular Weight
35136.1 Da
References
  1. Li J, Li YH, Yuan XR: Changes of phosphorylation of cAMP response element binding protein in rat nucleus accumbens after chronic ethanol intake: naloxone reversal. Acta Pharmacol Sin. 2003 Sep;24(9):930-6. [Article]
  2. Chartoff EH, Papadopoulou M, Konradi C, Carlezon WA Jr: Dopamine-dependent increases in phosphorylation of cAMP response element binding protein (CREB) during precipitated morphine withdrawal in primary cultures of rat striatum. J Neurochem. 2003 Oct;87(1):107-18. [Article]
  3. Gao C, Chen LW, Tao YM, Chen J, Xu XJ, Chi ZQ: Effects of ohmefentanyl stereoisomers on phosphorylation of cAMP- response element binding protein in cultured rat hippocampal neurons. Acta Pharmacol Sin. 2003 Dec;24(12):1253-8. [Article]
  4. Walters CL, Cleck JN, Kuo YC, Blendy JA: Mu-opioid receptor and CREB activation are required for nicotine reward. Neuron. 2005 Jun 16;46(6):933-43. [Article]
  5. Hawes JJ, Narasimhaiah R, Picciotto MR: Galanin attenuates cyclic AMP regulatory element-binding protein (CREB) phosphorylation induced by chronic morphine and naloxone challenge in Cath.a cells and primary striatal cultures. J Neurochem. 2006 Feb;96(4):1160-8. Epub 2006 Jan 17. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Antagonist
Other/unknown
General Function
Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa-B DNA-binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of the CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act synergistically with NF-kappa-B to activate transcription involving respective recruitment adjacent response elements; the function involves CREBBP. Can activate the transcriptional activity of TFF1. Also mediates membrane-initiated estrogen signaling involving various kinase cascades. Essential for MTA1-mediated transcriptional regulation of BRCA1 and BCAS3 (PubMed:17922032). Maintains neuronal survival in response to ischemic reperfusion injury when in the presence of circulating estradiol (17-beta-estradiol/E2) (By similarity)
Specific Function
14-3-3 protein binding
Gene Name
ESR1
Uniprot ID
P03372
Uniprot Name
Estrogen receptor
Molecular Weight
66215.45 Da
References
  1. Farooqui M, Geng ZH, Stephenson EJ, Zaveri N, Yee D, Gupta K: Naloxone acts as an antagonist of estrogen receptor activity in MCF-7 cells. Mol Cancer Ther. 2006 Mar;5(3):611-20. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Transmembrane receptor that functions as a pattern recognition receptor recognizing pathogen- and damage-associated molecular patterns (PAMPs and DAMPs) to induce innate immune responses via downstream signaling pathways (PubMed:10835634, PubMed:15809303, PubMed:16622205, PubMed:17292937, PubMed:17478729, PubMed:20037584, PubMed:20711192, PubMed:23880187, PubMed:27022195, PubMed:29038465). At the plasma membrane, cooperates with LY96 to mediate the innate immune response to bacterial lipopolysaccharide (LPS) (PubMed:27022195). Also involved in LPS-independent inflammatory responses triggered by free fatty acids, such as palmitate, and Ni(2+) (PubMed:20711192). Mechanistically, acts via MYD88, TIRAP and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response (PubMed:10835634, PubMed:21393102, PubMed:27022195, PubMed:36945827, PubMed:9237759). Alternatively, CD14-mediated TLR4 internalization via endocytosis is associated with the initiation of a MYD88-independent signaling via the TICAM1-TBK1-IRF3 axis leading to type I interferon production (PubMed:14517278). In addition to the secretion of proinflammatory cytokines, initiates the activation of NLRP3 inflammasome and formation of a positive feedback loop between autophagy and NF-kappa-B signaling cascade (PubMed:32894580). In complex with TLR6, promotes inflammation in monocytes/macrophages by associating with TLR6 and the receptor CD86 (PubMed:23880187). Upon ligand binding, such as oxLDL or amyloid-beta 42, the TLR4:TLR6 complex is internalized and triggers inflammatory response, leading to NF-kappa-B-dependent production of CXCL1, CXCL2 and CCL9 cytokines, via MYD88 signaling pathway, and CCL5 cytokine, via TICAM1 signaling pathway (PubMed:23880187). In myeloid dendritic cells, vesicular stomatitis virus glycoprotein G but not LPS promotes the activation of IRF7, leading to type I IFN production in a CD14-dependent manner (PubMed:15265881, PubMed:23880187). Required for the migration-promoting effects of ZG16B/PAUF on pancreatic cancer cells
Specific Function
amyloid-beta binding
Gene Name
TLR4
Uniprot ID
O00206
Uniprot Name
Toll-like receptor 4
Molecular Weight
95679.19 Da
References
  1. Lewis SS, Loram LC, Hutchinson MR, Li CM, Zhang Y, Maier SF, Huang Y, Rice KC, Watkins LR: (+)-naloxone, an opioid-inactive toll-like receptor 4 signaling inhibitor, reverses multiple models of chronic neuropathic pain in rats. J Pain. 2012 May;13(5):498-506. doi: 10.1016/j.jpain.2012.02.005. Epub 2012 Apr 20. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
General Function
Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs (PubMed:18762277, PubMed:7980644, PubMed:9169443, PubMed:9490062). Hydrolyzes aromatic and aliphatic esters, but has no catalytic activity toward amides or a fatty acyl-CoA ester (PubMed:18762277, PubMed:7980644, PubMed:9169443, PubMed:9490062). Hydrolyzes the methyl ester group of cocaine to form benzoylecgonine (PubMed:7980644). Catalyzes the transesterification of cocaine to form cocaethylene (PubMed:7980644). Displays fatty acid ethyl ester synthase activity, catalyzing the ethyl esterification of oleic acid to ethyloleate (PubMed:7980644). Converts monoacylglycerides to free fatty acids and glycerol. Hydrolyzes of 2-arachidonoylglycerol and prostaglandins (PubMed:21049984). Hydrolyzes cellular cholesteryl esters to free cholesterols and promotes reverse cholesterol transport (RCT) by facilitating both the initial and final steps in the process (PubMed:11015575, PubMed:16024911, PubMed:16971496, PubMed:18762277). First of all, allows free cholesterol efflux from macrophages to extracellular cholesterol acceptors and secondly, releases free cholesterol from lipoprotein-delivered cholesteryl esters in the liver for bile acid synthesis or direct secretion into the bile (PubMed:16971496, PubMed:18599737, PubMed:18762277)
Specific Function
carboxylesterase activity
Gene Name
CES1
Uniprot ID
P23141
Uniprot Name
Liver carboxylesterase 1
Molecular Weight
62520.62 Da
References
  1. Bencharit S, Morton CL, Xue Y, Potter PM, Redinbo MR: Structural basis of heroin and cocaine metabolism by a promiscuous human drug-processing enzyme. Nat Struct Biol. 2003 May;10(5):349-56. [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. Fang WB, Chang Y, McCance-Katz EF, Moody DE: Determination of naloxone and nornaloxone (noroxymorphone) by high-performance liquid chromatography-electrospray ionization- tandem mass spectrometry. J Anal Toxicol. 2009 Oct;33(8):409-17. doi: 10.1093/jat/33.8.409. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite's water solubility, thereby facilitating excretion into either the urine or bile (PubMed:12181437, PubMed:15472229, PubMed:18004206, PubMed:18004212, PubMed:18719240, PubMed:19830808, PubMed:23288867). Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds (PubMed:12181437, PubMed:18004206, PubMed:18004212). Catalyzes the glucuronidation of endogenous estrogen hormones such as estradiol, estrone and estriol (PubMed:15472229, PubMed:18719240, PubMed:23288867). Involved in the glucuronidation of bilirubin, a degradation product occurring in the normal catabolic pathway that breaks down heme in vertebrates (PubMed:17187418, PubMed:18004206, PubMed:19830808, PubMed:24525562). Also catalyzes the glucuronidation the isoflavones genistein, daidzein, glycitein, formononetin, biochanin A and prunetin, which are phytoestrogens with anticancer and cardiovascular properties (PubMed:18052087, PubMed:19545173). Involved in the glucuronidation of the AGTR1 angiotensin receptor antagonist losartan, a drug which can inhibit the effect of angiotensin II (PubMed:18674515). Involved in the biotransformation of 7-ethyl-10-hydroxycamptothecin (SN-38), the pharmacologically active metabolite of the anticancer drug irinotecan (PubMed:12181437, PubMed:18004212, PubMed:20610558)
Specific Function
enzyme binding
Gene Name
UGT1A1
Uniprot ID
P22309
Uniprot Name
UDP-glucuronosyltransferase 1A1
Molecular Weight
59590.91 Da
References
  1. Williams JA, Hyland R, Jones BC, Smith DA, Hurst S, Goosen TC, Peterkin V, Koup JR, Ball SE: Drug-drug interactions for UDP-glucuronosyltransferase substrates: a pharmacokinetic explanation for typically observed low exposure (AUCi/AUC) ratios. Drug Metab Dispos. 2004 Nov;32(11):1201-8. doi: 10.1124/dmd.104.000794. Epub 2004 Aug 10. [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. Fang WB, Chang Y, McCance-Katz EF, Moody DE: Determination of naloxone and nornaloxone (noroxymorphone) by high-performance liquid chromatography-electrospray ionization- tandem mass spectrometry. J Anal Toxicol. 2009 Oct;33(8):409-17. doi: 10.1093/jat/33.8.409. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
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. Fang WB, Chang Y, McCance-Katz EF, Moody DE: Determination of naloxone and nornaloxone (noroxymorphone) by high-performance liquid chromatography-electrospray ionization- tandem mass spectrometry. J Anal Toxicol. 2009 Oct;33(8):409-17. doi: 10.1093/jat/33.8.409. [Article]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
General Function
Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transporter in plasma, typically binds about 80% of all plasma zinc (PubMed:19021548). Major calcium and magnesium transporter in plasma, binds approximately 45% of circulating calcium and magnesium in plasma (By similarity). Potentially has more than two calcium-binding sites and might additionally bind calcium in a non-specific manner (By similarity). The shared binding site between zinc and calcium at residue Asp-273 suggests a crosstalk between zinc and calcium transport in the blood (By similarity). The rank order of affinity is zinc > calcium > magnesium (By similarity). Binds to the bacterial siderophore enterobactin and inhibits enterobactin-mediated iron uptake of E.coli from ferric transferrin, and may thereby limit the utilization of iron and growth of enteric bacteria such as E.coli (PubMed:6234017). Does not prevent iron uptake by the bacterial siderophore aerobactin (PubMed:6234017)
Specific Function
antioxidant activity
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Albumin
Molecular Weight
69365.94 Da
References
  1. FDA Approved Drug Products: Kloxxado (Naloxone) Nasal Spray [Link]
  2. FDA Approved Drug Products: Zubsolv (Buprenorphine, Naloxone) Sublingual Tablet [Link]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Na(+)-independent transporter that mediates the cellular uptake of a broad range of organic anions such as the endogenous bile salts cholate and deoxycholate, either in their unconjugated or conjugated forms (taurocholate and glycocholate), at the plasmam membrane (PubMed:19129463, PubMed:7557095). Responsible for intestinal absorption of bile acids (By similarity). Transports dehydroepiandrosterone 3-sulfate (DHEAS), a major circulating steroid secreted by the adrenal cortex, as well as estrone 3-sulfate and 17beta-estradiol 17-O-(beta-D-glucuronate) (PubMed:11159893, PubMed:12568656, PubMed:19129463, PubMed:23918469, PubMed:25560245, PubMed:9539145). Mediates apical uptake of all-trans-retinol (atROL) across human retinal pigment epithelium, which is essential to maintaining the integrity of the visual cycle and thus vision (PubMed:25560245). Involved in the uptake of clinically used drugs (PubMed:17301733, PubMed:20686826, PubMed:27777271). Capable of thyroid hormone transport (both T3 or 3,3',5'-triiodo-L-thyronine, and T4 or L-tyroxine) (PubMed:19129463, PubMed:20358049). Also transports prostaglandin E2 (PubMed:19129463). Plays roles in blood-brain and -cerebrospinal fluid barrier transport of organic anions and signal mediators, and in hormone uptake by neural cells (By similarity). May also play a role in the reuptake of neuropeptides such as substance P/TAC1 and vasoactive intestinal peptide/VIP released from retinal neurons (PubMed:25132355). May play an important role in plasma and tissue distribution of the structurally diverse chemotherapeutic drugs methotrexate and paclitaxel (PubMed:23243220). Shows a pH-sensitive substrate specificity which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment (PubMed:19129463). Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions (PubMed:19129463). May contribute to regulate the transport of organic compounds in testis across the blood-testis-barrier (Probable)
Specific Function
bile acid transmembrane transporter activity
Gene Name
SLCO1A2
Uniprot ID
P46721
Uniprot Name
Solute carrier organic anion transporter family member 1A2
Molecular Weight
74144.105 Da
References
  1. Gao B, Hagenbuch B, Kullak-Ublick GA, Benke D, Aguzzi A, Meier PJ: Organic anion-transporting polypeptides mediate transport of opioid peptides across blood-brain barrier. J Pharmacol Exp Ther. 2000 Jul;294(1):73-9. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
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. Mahar Doan KM, Humphreys JE, Webster LO, Wring SA, Shampine LJ, Serabjit-Singh CJ, Adkison KK, Polli JW: Passive permeability and P-glycoprotein-mediated efflux differentiate central nervous system (CNS) and non-CNS marketed drugs. J Pharmacol Exp Ther. 2002 Dec;303(3):1029-37. [Article]

Drug created at June 13, 2005 13:24 / Updated at October 03, 2024 22:14