DB00486 - Nabilone
| Identification | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Name | Nabilone | ||||||||
| Accession Number | DB00486 (APRD01127) | ||||||||
| Type | small molecule | ||||||||
| Description | Nabilone is a synthetic cannabinoid with therapeutic use as an antiemetic and as an adjunct analgesic for neuropathic pain. It is a synthetic cannabinoid, which mimics the main ingredient of marijuana (THC) but it has more predictable side effects and causes no or minimal euphoria. Nabilone is not derived from the cannabis plant as is dronabinol. 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. Although it doesn't have the official indication (except in Mexico), nabilone is widely used as an adjunct therapy for chronic pain management. Numerous trials and case studies have demonstrate various benefits for condition such as fibromyalgia and multiple scerosis. Nabilone is a racemate consisting of the (S,S) and the (R,R) isomers ("trans"). | ||||||||
| Structure |
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| Categories (*) | |||||||||
| Molecular Weight | 372.5408 | ||||||||
| Groups | approved | ||||||||
| Monoisotopic Weight | 372.266445018 | ||||||||
| Pharmacology | |||||||||
| Indication | Used for the control of nausea and vomiting, caused by chemotherapeutic agents used in the treatment of cancer, in patients who have failed to respond adequately to conventional antiemetic treatments. | ||||||||
| Mechanism of action | The mode of action of nabilone has been studied in cats and dogs. Although its anti-emetic action is not yet fully understood, it is apparent that there are a number of points in the control systems of the body at which Nabilone could block the emetic mechanism. It is likely that nabilone exerts its actions via binding to the cannabinoid receptors. | ||||||||
| Absorption | Rapidly absorbed from the gastrointestinal tract following oral administration. | ||||||||
| Protein binding | Not Available | ||||||||
| Biotransformation | 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). Therefore, it appears that the major excretory pathway is the biliary system. | ||||||||
| 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. | ||||||||
| Affected organisms |
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| Interactions | |||||||||
| Drug Interactions |
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Targets
| Cannabinoid receptor 2 | |
|---|---|
| Name | Cannabinoid receptor 2 |
| Gene Name | CNR2 |
| Pharmacological action | yes |
| Actions | partial agonist |
| References |
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| DTHybrid score | 0.8684 |
| Cannabinoid receptor 1 | |
| Name | Cannabinoid receptor 1 |
| Gene Name | CNR1 |
| Pharmacological action | yes |
| Actions | partial agonist |
| References |
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| DTHybrid score | 1.0028 |
Predictions
| Id | Partner name | Gene Name | Score |
|---|---|---|---|
| 4512 | Cytochrome P450 3A4 | CYP3A4 | 0.0981 |
| 5718 | Cytochrome P450 2A6 | CYP2A6 | 0.0469 |
| 1732 | ATP-binding cassette sub-family G member 2 | ABCG2 | 0.0453 |
| 6024 | Cytochrome P450 1A1 | CYP1A1 | 0.0449 |
| 20 | Prostaglandin G/H synthase 1 | PTGS1 | 0.0446 |
| 6016 | Cytochrome P450 2C19 | CYP2C19 | 0.0378 |
| 4757 | Cytochrome P450 2C9 | CYP2C9 | 0.0358 |
| 1588 | Multidrug resistance protein 1 | ABCB1 | 0.0355 |