Mecamylamine
From Wikipedia
| Systematic (IUPAC) name | |
|---|---|
| (2R)-N,2,3,3-tetramethylbicyclo[2.2.1]heptan-2-amine | |
| Identifiers | |
| CAS number | 60-40-2 |
| ATC code | C02BB01 |
| PubChem | 4032 |
| DrugBank | APRD00458 |
| Chemical data | |
| Formula | C11H21N |
| Mol. mass | 167.291 g/mol |
| SMILES | eMolecules & PubChem |
| Pharmacokinetic data | |
| Bioavailability | ? |
| Protein binding | 40% |
| Metabolism | ? |
| Half life | ? |
| Excretion | ? |
| Therapeutic considerations | |
| Pregnancy cat. | ? |
| Legal status | ℞ Prescription only |
| Routes | Oral |
| (what is this?) (verify) | |
Mecamylamine is a voltage dependent non-competitive antagonist at nicotinic receptors. It is well absorbed from the gastrointestinal tract and crosses the blood-brain barrier.
Uses
Mecamylamine has been used as a ganglionic blocker in treating hypertension, but, like most ganglionic blockers, is more often used now as a research tool.
Mecamylamine is also sometimes used as an anti-addictive drug to help people stop smoking tobacco,[1] and is now more widely used for this application than it is for lowering blood pressure. This effect is thought to be due to it blocking α3β4 nicotinic receptors in the brain.
In a recent double-blind, placebo controlled trial in patients with major depression, S-mecamylamine appears to have efficacy as an augmentation therapy. This was the first substantive evidence that compounds where the primary pharmacology is antagonism to neuronal nicotinic receptors will have antidepressant properties.[2][3]
S-(+)-mecamylamine dissociates more slowly from alpha-4 beta-2 and alpha-3 beta-4 receptors than does the R-(-)-enantiomer.[4] The pKa value is 11.2.
A small SAR study was undertaken by Suchocki et al.[5]
References
- ↑ Shytle RD, Penny E, Silver AA, Goldman J, Sanberg PR (July 2002). "Mecamylamine (Inversine): an old antihypertensive with new research directions". J Hum Hypertens 16 (7): 453–7. doi:. PMID 12080428. http://dx.doi.org/10.1038/sj.jhh.1001416.
- ↑ Lippiello PM, Beaver JS, Gatto GJ, et al (2008). [Expression error: Missing operand for > "TC-5214 (S-(+)-mecamylamine): a neuronal nicotinic receptor modulator with antidepressant activity"]. CNS Neurosci Ther 14 (4): 266–77. doi:. PMID 19040552.
- ↑ Rabenstein RL, Caldarone BJ, Picciotto MR (December 2006). [Expression error: Missing operand for > "The nicotinic antagonist mecamylamine has antidepressant-like effects in wild-type but not beta2- or alpha7-nicotinic acetylcholine receptor subunit knockout mice"]. Psychopharmacology (Berl.) 189 (3): 395–401. doi:. PMID 17016705.
- ↑ Papke RL, Sanberg PR, Shytle RD (May 2001). "Analysis of mecamylamine stereoisomers on human nicotinic receptor subtypes". J. Pharmacol. Exp. Ther. 297 (2): 646–56. PMID 11303054. http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=11303054.
- ↑ JMC 1991
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