DB01273 - Varenicline
| Identification | |
|---|---|
| Name | Varenicline |
| Accession Number | DB01273 |
| Type | small molecule |
| Description | Varenicline is a prescription medication used to treat smoking addiction. This medication is the first approved nicotinic receptor partial agonist. Specifically, varenicline is a partial agonist of the alpha4/beta2 subtype of the nicotinic acetylcholine receptor. In addition it acts on alpha3/beta4 and weakly on alpha3beta2 and alpha6-containing receptors. A full agonism was displayed on alpha7-receptors. |
| Structure |
|
| Categories (*) | |
| Molecular Weight | 211.2624 |
| Groups | approved |
| Monoisotopic Weight | 211.110947431 |
| Pharmacology | |
| Indication | For use as an aid in smoking cessation. |
| Mechanism of action | Varenicline is an alpha-4 beta-2 neuronal nicotinic acetylcholine receptor partial agonist. The drug shows high selectiviyty for this receptor subclass, relative to other nicotinic receptors (>500-fold alpha-3 beta-4, >3500-fold alpha-7, >20,000-fold alpha-1 beta gamma delta) or non-nicotinic receptors and transporters (>2000-fold). The drug competitively inhibits the ability of nicotine to bind to and activate the alpha-4 beta-2 receptor. The drug exerts mild agonistic activity at this site, though at a level much lower than nicotine; it is presumed that this activation eases withdrawal symptoms. |
| Absorption | Not Available |
| Protein binding | Less than 20%. |
| Biotransformation | Metabolism is limited (<10%). Most of the active compound is excreted renally (81%). A small proportion is glucuronidated, oxidated, N-formylated or conjugated to a hexose. |
| Route of elimination | Varenicline undergoes minimal metabolism, with 92% excreted unchanged in the urine. Renal elimination of varenicline is primarily through glomerular filtration along with active tubular secretion possibly via the organic cation transporter, OCT2. |
| Toxicity | Not Available |
| Affected organisms |
|
| Interactions | |
| Drug Interactions | Not Available |
| Food Interactions | Not Available |
Targets
| Neuronal acetylcholine receptor subunit alpha-4 | |
|---|---|
| Name | Neuronal acetylcholine receptor subunit alpha-4 |
| Gene Name | CHRNA4 |
| Pharmacological action | yes |
| Actions | partial agonist |
| References |
|
| DTHybrid score | 0.3986 |
| Neuronal acetylcholine receptor subunit alpha-7 | |
| Name | Neuronal acetylcholine receptor subunit alpha-7 |
| Gene Name | CHRNA7 |
| Pharmacological action | unknown |
| Actions | agonist |
| References |
|
| DTHybrid score | 0.3934 |
| Neuronal acetylcholine receptor subunit alpha-3 | |
| Name | Neuronal acetylcholine receptor subunit alpha-3 |
| Gene Name | CHRNA3 |
| Pharmacological action | unknown |
| Actions | partial agonist |
| References |
|
| DTHybrid score | 0.4736 |
| Neuronal acetylcholine receptor subunit alpha-6 | |
| Name | Neuronal acetylcholine receptor subunit alpha-6 |
| Gene Name | CHRNA6 |
| Pharmacological action | unknown |
| Actions | partial agonist |
| References |
|
| DTHybrid score | 0.3189 |