Nabilone
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Identification
- Summary
Nabilone is a synthetic delta-9-THC used in the treatment of anorexia and weight loss in HIV patients as well as nausea and vomiting in cancer chemotherapy.
- Brand Names
- Cesamet
- Generic Name
- Nabilone
- DrugBank Accession Number
- DB00486
- Background
Nabilone (marketed as Cesamet) is a synthetic form of delta-9-tetrahydrocannabinol (Δ⁹-THC), the primary psychoactive component of cannabis (marijuana). Although structurally distinct from THC, nabilone mimics THC's structure and pharmacological activity through weak partial agonist activity at Cannabinoid-1 (CB1R) and Cannabinoid-2 (CB2R) receptors, however it is considered to be twice as active as Δ⁹-THC. Nabilone is approved by the FDA for the treatment of nausea and vomiting associated with cancer chemotherapy in patients who have failed to respond adequately to conventional antiemetic treatments Label.
Tetrahydrocannabinol (THC) and cannabidiol (CBD) are the two most abundant cannabinoids found naturally in the resin of the marijuana plant, both of which are pharmacologically active due to their interaction with cannabinoid receptors that are found throughout the body 5. While both CBD and THC are used for medicinal purposes, they have different receptor activity, function, and physiological effects. If not provided in their activated form (such as through synthetic forms like Nabilone or Dronabinol), THC and CBD are obtained through conversion from their precursors, tetrahydrocannabinolic acid-A (THCA-A) and cannabidiolic acid (CBDA), through decarboxylation reactions. This can be achieved through heating, smoking, vaporization, or baking of dried unfertilized female cannabis flowers.
From a pharmacological perspective, Cannabis' diverse receptor profile explains its potential application for such a wide variety of medical conditions. Cannabis contains more than 400 different chemical compounds, of which 61 are considered cannabinoids, a class of compounds that act upon endogenous cannabinoid receptors of the body 6. The endocannabinoid system is widely distributed throughout the central and peripheral nervous system (via the Cannabinoid Receptors CB1 and CB2) and plays a role in many physiological processes such as inflammation, cardiovascular function, learning, pain, memory, stress and emotional regulation, and the sleep/wake cycle among many others 7. CB1 receptors are found in both the central and peripheral nervous system, and are most abundant in the hippocampus and amygdala, which are the areas of the brain responsible for short-term memory storage and emotional regulation. CB2 receptors are mainly located in the peripheral nervous system and can be found on lymphoid tissue where they are involved in regulation of immune function 8.
In Canada, the United States, the United Kingdom and Mexico, nabilone is marketed as Cesamet. It was approved in 1985 by the United States FDA for treatment of chemotherapy-induced nausea and vomiting that has not responded to conventional antiemetics. Though it was approved by the FDA in 1985, the drug only began marketing in the United States in 2006. It is also approved for use in treatment of anorexia and weight loss in patients with AIDS.
Nabilone is a racemate consisting of the (S,S) and the (R,R) isomers.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
- Weight
- Average: 372.5408
Monoisotopic: 372.266445018 - Chemical Formula
- C24H36O3
- Synonyms
- Nabilon
- Nabilona
- Nabilone
- Nabilonum
- External IDs
- Cpd 109514
- LY 109 514
Pharmacology
- Indication
Nabilone is indicated for the treatment of the nausea and vomiting associated with cancer chemotherapy in patients who have failed to respond adequately to conventional antiemetic treatments. This restriction is required because a substantial proportion of any group of patients treated with Nabilone can be expected to experience disturbing psychotomimetic reactions not observed with other antiemetic agents.
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Refractory chemotherapy-induced nausea and vomiting (cinv) •••••••••••• ••••••• - Contraindications & Blackbox Warnings
- Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API
- Pharmacodynamics
Nabilone is a cannabinoid with therapeutic uses. It is an analog of dronabinol (also known as tetrahydrocannabinol or THC), the psychoactive ingredient in cannabis. Although structurally distinct from THC, nabilone mimics THC's structure and pharmacological activity through weak partial agonist activity at Cannabinoid-1 (CB1R) and Cannabinoid-2 (CB2R) receptors, however it is considered to be twice as active as Δ⁹-THC.
- Mechanism of action
Nabilone is an orally active synthetic cannabinoid which, like other cannabinoids, has complex effects on the central nervous system (CNS). It has been suggested that the antiemetic effect of nabilone is caused by interaction with the cannabinoid receptor system, i.e., the CB (1) receptor, which is a component of the endocannabinoid system of the body.
The endocannabinoid system is widely distributed throughout the central and peripheral nervous system (via the Cannabinoid Receptors CB1 and CB2) and plays a role in many physiological processes such as inflammation, cardiovascular function, learning, pain, memory, stress and emotional regulation, and the sleep/wake cycle among many others 7. CB1 receptors are found in both the central and peripheral nervous system, and are most abundant in the hippocampus and amygdala, which are the areas of the brain responsible for short-term memory storage and emotional regulation. CB2 receptors are mainly located in the peripheral nervous system and can be found on lymphoid tissue where they are involved in regulation of immune function 8.
Target Actions Organism ACannabinoid receptor 2 partial agonistHumans ACannabinoid receptor 1 partial agonistHumans - Absorption
Nabilone appears to be completely absorbed from the human gastrointestinal tract when administered orally. Following oral administration of a 2 mg dose of radiolabeled nabilone, peak plasma concentrations of approximately 2 ng/mL nabilone and 10 ng equivalents/mL total radioactivity are achieved within 2.0 hours.
- Volume of distribution
The apparent volume of distribution of nabilone is about 12.5 L/kg.
- Protein binding
Not Available
- Metabolism
Hepatic. Two metabolic pathways have been suggested. The major pathway probably involves the direct oxidation of Nabilone to produce hydroxylic and carboxylic analogues. These compounds are thought to account for the remaining plasma radioactivity when carbinol metabolites have been extracted.
- Route of elimination
The route and rate of the elimination of nabilone and its metabolites are similar to those observed with other cannabinoids, including delta-9-THC (dronabinol). When nabilone is administered intravenously, the drug and its metabolites are eliminated mainly in the feces (approximately 67%) and to a lesser extent in the urine (approximately 22%) within 7 days. Of the 67% recovered from the feces, 5% corresponded to the parent compound and 16% to its carbinol metabolite. Following oral administration about 60% of nabilone and its metabolites were recovered in the feces and about 24% in urine. Therefore, it appears that the major excretory pathway is the biliary system.
- Half-life
The plasma half-life (T1/2) values for nabilone and total radioactivity of identified and unidentified metabolites are about 2 and 35 hours, respectively.
- Clearance
Not Available
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- Toxicity
Symptoms of overdose include difficulty in breathing, hallucinations, mental changes (severe), nervousness or anxiety (severe). Monkeys treated with Nabilone at doses as high as 2mg/kg/day for a year experienced no significant adverse events. This result contrasts with the finding in a planned 1-year dog study that was prematurely terminated because of deaths associated with convulsions in dogs receiving as little as 0.5mg/kg/day. The earliest deaths, however, occurred at 56 days in dogs receiving 2mg/kg/day. The unusual vulnerability of the dog is not understood; it is hypothesised, however, that the explanation lies in the fact that the dog differs markedly from other species (including humans) in its metabolism of Nabilone.
- Pathways
- Not Available
- 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.
Drug Interaction Integrate drug-drug
interactions in your software1,2-Benzodiazepine Nabilone may increase the central nervous system depressant (CNS depressant) activities of 1,2-Benzodiazepine. Abaloparatide The risk or severity of adverse effects can be increased when Nabilone is combined with Abaloparatide. Abametapir The serum concentration of Nabilone can be increased when it is combined with Abametapir. Abatacept The metabolism of Nabilone can be increased when combined with Abatacept. Abrocitinib The metabolism of Abrocitinib can be decreased when combined with Nabilone. - Food Interactions
- Avoid alcohol.
- Take with or without food. Food does not significantly affect absorption.
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- International/Other Brands
- Nabilone (Meda)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Cesamet Capsule 1 mg/1 Oral Valeant Pharmaceuticals North America 2009-11-01 2017-11-13 US Cesamet Capsule 1 mg/1 Oral Bausch Health, Canada Inc. 2020-03-09 Not applicable US Cesamet Capsule 1 mg/1 Oral Valeant Pharmaceuticals North America 2017-11-12 2017-11-13 US Cesamet Capsule 1 mg/1 Oral Meda Pharma S.P.A. 2010-03-01 2020-03-31 US
Categories
- ATC Codes
- A04AD11 — Nabilone
- Drug Categories
- Agents producing tachycardia
- Alimentary Tract and Metabolism
- Antiemetics
- Antiemetics and Antinauseants
- Autonomic Agents
- Cannabinoids and similars
- Central Nervous System Agents
- Central Nervous System Depressants
- Cytochrome P-450 CYP2C8 Inhibitors
- Cytochrome P-450 CYP2C8 Inhibitors (moderate)
- Cytochrome P-450 CYP2C8 Substrates
- Cytochrome P-450 CYP2C9 Inhibitors
- Cytochrome P-450 CYP2C9 Inhibitors (moderate)
- Cytochrome P-450 CYP2C9 Substrates
- Cytochrome P-450 CYP2E1 Inhibitors
- Cytochrome P-450 CYP2E1 Inhibitors (weak)
- Cytochrome P-450 CYP2E1 Substrates
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors (weak)
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Drugs causing inadvertant photosensitivity
- Gastrointestinal Agents
- Hypotensive Agents
- Miscellaneous Antiemetics
- Peripheral Nervous System Agents
- Photosensitizing Agents
- Psychotropic Drugs
- Terpenes
- Tranquilizing Agents
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as naphthopyranones. These are compounds containing a naphthopyran skeleton where a ring carbon bears a carboxylic acid group. Naphthtopyran is made up of the pyran ring fused to a naphthalene ring system.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Naphthopyrans
- Sub Class
- Naphthopyranones
- Direct Parent
- Naphthopyranones
- Alternative Parents
- 2,2-dimethyl-1-benzopyrans / Alkyl aryl ethers / 1-hydroxy-4-unsubstituted benzenoids / 1-hydroxy-2-unsubstituted benzenoids / Cyclic ketones / Oxacyclic compounds / Organic oxides / Hydrocarbon derivatives
- Substituents
- 1-benzopyran / 1-hydroxy-2-unsubstituted benzenoid / 1-hydroxy-4-unsubstituted benzenoid / 2,2-dimethyl-1-benzopyran / Alkyl aryl ether / Aromatic heteropolycyclic compound / Benzenoid / Benzopyran / Carbonyl group / Chromane
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 2N4O9L084N
- CAS number
- 51022-71-0
- InChI Key
- GECBBEABIDMGGL-RTBURBONSA-N
- InChI
- InChI=1S/C24H36O3/c1-6-7-8-9-12-23(2,3)16-13-20(26)22-18-15-17(25)10-11-19(18)24(4,5)27-21(22)14-16/h13-14,18-19,26H,6-12,15H2,1-5H3/t18-,19-/m1/s1
- IUPAC Name
- (6aR,10aR)-1-hydroxy-6,6-dimethyl-3-(2-methyloctan-2-yl)-6H,6aH,7H,8H,9H,10H,10aH-benzo[c]isochromen-9-one
- SMILES
- [H][C@@]12CC(=O)CC[C@@]1([H])C(C)(C)OC1=CC(=CC(O)=C21)C(C)(C)CCCCCC
References
- General References
- Cunningham D, Bradley CJ, Forrest GJ, Hutcheon AW, Adams L, Sneddon M, Harding M, Kerr DJ, Soukop M, Kaye SB: A randomized trial of oral nabilone and prochlorperazine compared to intravenous metoclopramide and dexamethasone in the treatment of nausea and vomiting induced by chemotherapy regimens containing cisplatin or cisplatin analogues. Eur J Cancer Clin Oncol. 1988 Apr;24(4):685-9. [Article]
- Niiranen A, Mattson K: Antiemetic efficacy of nabilone and dexamethasone: a randomized study of patients with lung cancer receiving chemotherapy. Am J Clin Oncol. 1987 Aug;10(4):325-9. [Article]
- Herman TS, Einhorn LH, Jones SE, Nagy C, Chester AB, Dean JC, Furnas B, Williams SD, Leigh SA, Dorr RT, Moon TE: Superiority of nabilone over prochlorperazine as an antiemetic in patients receiving cancer chemotherapy. N Engl J Med. 1979 Jun 7;300(23):1295-7. [Article]
- Einhorn LH, Nagy C, Furnas B, Williams SD: Nabilone: an effective antiemetic in patients receiving cancer chemotherapy. J Clin Pharmacol. 1981 Aug-Sep;21(8-9 Suppl):64S-69S. [Article]
- Elsohly MA, Slade D: Chemical constituents of marijuana: the complex mixture of natural cannabinoids. Life Sci. 2005 Dec 22;78(5):539-48. doi: 10.1016/j.lfs.2005.09.011. Epub 2005 Sep 30. [Article]
- Sharma P, Murthy P, Bharath MM: Chemistry, metabolism, and toxicology of cannabis: clinical implications. Iran J Psychiatry. 2012 Fall;7(4):149-56. [Article]
- Baron EP: Comprehensive Review of Medicinal Marijuana, Cannabinoids, and Therapeutic Implications in Medicine and Headache: What a Long Strange Trip It's Been .... Headache. 2015 Jun;55(6):885-916. doi: 10.1111/head.12570. Epub 2015 May 25. [Article]
- Kaur R, Ambwani SR, Singh S: Endocannabinoid System: A Multi-Facet Therapeutic Target. Curr Clin Pharmacol. 2016;11(2):110-7. [Article]
- FDA Approved Drug Products: Cesamet (nabilone) capsules for oral use [Link]
- External Links
- Human Metabolome Database
- HMDB0014629
- KEGG Drug
- D05099
- PubChem Compound
- 5284592
- PubChem Substance
- 46505171
- ChemSpider
- 4447641
- BindingDB
- 50287941
- 31447
- ChEMBL
- CHEMBL947
- ZINC
- ZINC000001542930
- Therapeutic Targets Database
- DAP000067
- PharmGKB
- PA164746998
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Nabilone
- FDA label
- Download (94.9 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 Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Completed Not Available Failed Back Surgery Syndrome 1 somestatus stop reason just information to hide Not Available Completed Treatment Fibromyalgia / Sleep Initiation and Maintenance Disorders 1 somestatus stop reason just information to hide Not Available Not Yet Recruiting Supportive Care Inflammatory Bowel Diseases (IBD) 1 somestatus stop reason just information to hide 4 Completed Treatment Antineoplastic Combined Chemotherapy Protocols / Peripheral neuropathy 1 somestatus stop reason just information to hide 4 Completed Treatment Diabetic Neuropathies 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Meda pharmaceuticals inc
- Packagers
- Meda AB
- Valeant Ltd.
- Dosage Forms
Form Route Strength Capsule Oral 0.25 mg Capsule Oral 0.5 mg Capsule Oral 1 mg Capsule Oral 1 mg/1 Capsule Oral 1.0 mg - Prices
Unit description Cost Unit Cesamet 1 mg capsule 13.99USD capsule Cesamet 0.5 mg Capsule 3.49USD capsule DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source logP 6.8 Not Available - Predicted Properties
Property Value Source Water Solubility 0.000493 mg/mL ALOGPS logP 7.5 ALOGPS logP 6.36 Chemaxon logS -5.9 ALOGPS pKa (Strongest Acidic) 9.33 Chemaxon pKa (Strongest Basic) -4.9 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 3 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 46.53 Å2 Chemaxon Rotatable Bond Count 6 Chemaxon Refractivity 110.2 m3·mol-1 Chemaxon Polarizability 44.91 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9954 Blood Brain Barrier + 0.9575 Caco-2 permeable + 0.7787 P-glycoprotein substrate Substrate 0.8103 P-glycoprotein inhibitor I Non-inhibitor 0.7926 P-glycoprotein inhibitor II Inhibitor 0.6054 Renal organic cation transporter Non-inhibitor 0.836 CYP450 2C9 substrate Non-substrate 0.7385 CYP450 2D6 substrate Non-substrate 0.8433 CYP450 3A4 substrate Substrate 0.6842 CYP450 1A2 substrate Non-inhibitor 0.6601 CYP450 2C9 inhibitor Non-inhibitor 0.714 CYP450 2D6 inhibitor Non-inhibitor 0.9059 CYP450 2C19 inhibitor Non-inhibitor 0.6521 CYP450 3A4 inhibitor Non-inhibitor 0.8654 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.7642 Ames test Non AMES toxic 0.8337 Carcinogenicity Non-carcinogens 0.8598 Biodegradation Not ready biodegradable 0.9948 Rat acute toxicity 2.5397 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9159 hERG inhibition (predictor II) Non-inhibitor 0.7654
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS splash10-0a6s-4059000000-d86f1fa9d2fb7b5aeb43 Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-00di-7019000000-1af180004615c75bf98e Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-00di-0009000000-9a67fce848ab43c6e760 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-00di-0009000000-6662a9a158936e8d1fee Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-000i-5098000000-e1a2e4e0d120c5eac933 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-05g1-0089000000-ae181a8f3b1e4eb0ce22 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-0536-9021000000-ba8ae26d7564526c5aad Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 208.248468 predictedDarkChem Lite v0.1.0 [M-H]- 208.497168 predictedDarkChem Lite v0.1.0 [M-H]- 199.06223 predictedDeepCCS 1.0 (2019) [M+H]+ 208.197468 predictedDarkChem Lite v0.1.0 [M+H]+ 208.504968 predictedDarkChem Lite v0.1.0 [M+H]+ 201.4578 predictedDeepCCS 1.0 (2019) [M+Na]+ 208.239868 predictedDarkChem Lite v0.1.0 [M+Na]+ 207.37032 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Partial agonist
- General Function
- Heterotrimeric G protein-coupled receptor for endocannabinoid 2-arachidonoylglycerol mediating inhibition of adenylate cyclase. May function in inflammatory response, nociceptive transmission and bone homeostasis
- Specific Function
- cannabinoid receptor activity
- Gene Name
- CNR2
- Uniprot ID
- P34972
- Uniprot Name
- Cannabinoid receptor 2
- Molecular Weight
- 39680.275 Da
References
- Conti S, Costa B, Colleoni M, Parolaro D, Giagnoni G: Antiinflammatory action of endocannabinoid palmitoylethanolamide and the synthetic cannabinoid nabilone in a model of acute inflammation in the rat. Br J Pharmacol. 2002 Jan;135(1):181-7. [Article]
- Mendizabal VE, Adler-Graschinsky E: Cannabinoids as therapeutic agents in cardiovascular disease: a tale of passions and illusions. Br J Pharmacol. 2007 Jun;151(4):427-40. Epub 2007 Apr 23. [Article]
- Davis M, Maida V, Daeninck P, Pergolizzi J: The emerging role of cannabinoid neuromodulators in symptom management. Support Care Cancer. 2007 Jan;15(1):63-71. Epub 2006 Dec 1. [Article]
- Kraft B, Kress HG: [Cannabinoids and the immune system. Of men, mice and cells]. Schmerz. 2004 Jun;18(3):203-10. [Article]
- Darmani NA: The cannabinoid CB1 receptor antagonist SR 141716A reverses the antiemetic and motor depressant actions of WIN 55, 212-2. Eur J Pharmacol. 2001 Oct 26;430(1):49-58. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Partial agonist
- General Function
- G-protein coupled receptor for endogenous cannabinoids (eCBs), including N-arachidonoylethanolamide (also called anandamide or AEA) and 2-arachidonoylglycerol (2-AG), as well as phytocannabinoids, such as delta(9)-tetrahydrocannabinol (THC) (PubMed:15620723, PubMed:27768894, PubMed:27851727). Mediates many cannabinoid-induced effects, acting, among others, on food intake, memory loss, gastrointestinal motility, catalepsy, ambulatory activity, anxiety, chronic pain. Signaling typically involves reduction in cyclic AMP (PubMed:1718258, PubMed:21895628, PubMed:27768894). In the hypothalamus, may have a dual effect on mitochondrial respiration depending upon the agonist dose and possibly upon the cell type. Increases respiration at low doses, while decreases respiration at high doses. At high doses, CNR1 signal transduction involves G-protein alpha-i protein activation and subsequent inhibition of mitochondrial soluble adenylate cyclase, decrease in cyclic AMP concentration, inhibition of protein kinase A (PKA)-dependent phosphorylation of specific subunits of the mitochondrial electron transport system, including NDUFS2. In the hypothalamus, inhibits leptin-induced reactive oxygen species (ROS) formation and mediates cannabinoid-induced increase in SREBF1 and FASN gene expression. In response to cannabinoids, drives the release of orexigenic beta-endorphin, but not that of melanocyte-stimulating hormone alpha/alpha-MSH, from hypothalamic POMC neurons, hence promoting food intake. In the hippocampus, regulates cellular respiration and energy production in response to cannabinoids. Involved in cannabinoid-dependent depolarization-induced suppression of inhibition (DSI), a process in which depolarization of CA1 postsynaptic pyramidal neurons mobilizes eCBs, which retrogradely activate presynaptic CB1 receptors, transiently decreasing GABAergic inhibitory neurotransmission. Also reduces excitatory synaptic transmission (By similarity). In superior cervical ganglions and cerebral vascular smooth muscle cells, inhibits voltage-gated Ca(2+) channels in a constitutive, as well as agonist-dependent manner (PubMed:17895407). In cerebral vascular smooth muscle cells, cannabinoid-induced inhibition of voltage-gated Ca(2+) channels leads to vasodilation and decreased vascular tone (By similarity). Induces leptin production in adipocytes and reduces LRP2-mediated leptin clearance in the kidney, hence participating in hyperleptinemia. In adipose tissue, CNR1 signaling leads to increased expression of SREBF1, ACACA and FASN genes (By similarity). In the liver, activation by endocannabinoids leads to increased de novo lipogenesis and reduced fatty acid catabolism, associated with increased expression of SREBF1/SREBP-1, GCK, ACACA, ACACB and FASN genes. May also affect de novo cholesterol synthesis and HDL-cholesteryl ether uptake. Peripherally modulates energy metabolism (By similarity). In high carbohydrate diet-induced obesity, may decrease the expression of mitochondrial dihydrolipoyl dehydrogenase/DLD in striated muscles, as well as that of selected glucose/ pyruvate metabolic enzymes, hence affecting energy expenditure through mitochondrial metabolism (By similarity). In response to cannabinoid anandamide, elicits a pro-inflammatory response in macrophages, which involves NLRP3 inflammasome activation and IL1B and IL18 secretion (By similarity). In macrophages infiltrating pancreatic islets, this process may participate in the progression of type-2 diabetes and associated loss of pancreatic beta-cells (PubMed:23955712)
- Specific Function
- cannabinoid receptor activity
- Gene Name
- CNR1
- Uniprot ID
- P21554
- Uniprot Name
- Cannabinoid receptor 1
- Molecular Weight
- 52857.365 Da
References
- Davis M, Maida V, Daeninck P, Pergolizzi J: The emerging role of cannabinoid neuromodulators in symptom management. Support Care Cancer. 2007 Jan;15(1):63-71. Epub 2006 Dec 1. [Article]
- Darmani NA: The cannabinoid CB1 receptor antagonist SR 141716A reverses the antiemetic and motor depressant actions of WIN 55, 212-2. Eur J Pharmacol. 2001 Oct 26;430(1):49-58. [Article]
- Hirst RA, Almond SL, Lambert DG: Characterisation of the rat cerebella CB1 receptor using SR141716A, a central cannabinoid receptor antagonist. Neurosci Lett. 1996 Dec 13;220(2):101-4. [Article]
- Pertwee RG: Cannabis and cannabinoids: pharmacology and rationale for clinical use. Forsch Komplementarmed. 1999 Oct;6 Suppl 3:12-5. [Article]
- Pertwee RG, Fernando SR: Evidence for the presence of cannabinoid CB1 receptors in mouse urinary bladder. Br J Pharmacol. 1996 Aug;118(8):2053-8. [Article]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- SubstrateInhibitor
- 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
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- 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
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- SubstrateInhibitor
- 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
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- SubstrateInhibitor
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of fatty acids (PubMed:10553002, PubMed:18577768). 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:10553002, PubMed:18577768). Catalyzes the hydroxylation of carbon-hydrogen bonds. Hydroxylates fatty acids specifically at the omega-1 position displaying the highest catalytic activity for saturated fatty acids (PubMed:10553002, PubMed:18577768). May be involved in the oxidative metabolism of xenobiotics (Probable)
- Specific Function
- 4-nitrophenol 2-monooxygenase activity
- Gene Name
- CYP2E1
- Uniprot ID
- P05181
- Uniprot Name
- Cytochrome P450 2E1
- Molecular Weight
- 56848.42 Da
References
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of polyunsaturated fatty acids (PUFA) in the cardiovascular system (PubMed:19965576, PubMed:8631948). 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:19965576, PubMed:8631948). Catalyzes the epoxidation of double bonds of PUFA (PubMed:19965576, PubMed:8631948). Converts arachidonic acid to four regioisomeric epoxyeicosatrienoic acids (EpETrE), likely playing a major role in the epoxidation of endogenous cardiac arachidonic acid pools (PubMed:8631948). In endothelial cells, participates in eicosanoids metabolism by converting hydroperoxide species into hydroxy epoxy metabolites. In combination with 15-lipoxygenase metabolizes arachidonic acid and converts hydroperoxyicosatetraenoates (HpETEs) into hydroxy epoxy eicosatrienoates (HEETs), which are precursors of vasodilatory trihydroxyicosatrienoic acids (THETAs). This hydroperoxide isomerase activity is NADPH- and O2-independent (PubMed:19737933). Catalyzes the monooxygenation of a various xenobiotics, such as danazol, amiodarone, terfenadine, astemizole, thioridazine, tamoxifen, cyclosporin A and nabumetone (PubMed:19923256). Catalyzes hydroxylation of the anthelmintics albendazole and fenbendazole (PubMed:23959307). Catalyzes the sulfoxidation of fenbedazole (PubMed:19923256)
- Specific Function
- arachidonic acid 11,12-epoxygenase activity
- Gene Name
- CYP2J2
- Uniprot ID
- P51589
- Uniprot Name
- Cytochrome P450 2J2
- Molecular Weight
- 57610.165 Da
References
- Kocis PT, Vrana KE: Delta-9-Tetrahydrocannabinol and Cannabidiol Drug-Drug Interactions. Med Cannabis Cannabinoids. 2020 Jul 7;3(1):61-73. doi: 10.1159/000507998. eCollection 2020 Aug. [Article]
Drug created at June 13, 2005 13:24 / Updated at October 29, 2024 18:01