Mecamylamine (
INN,
BAN
Ban, or BAN, may refer to:
Law
* Ban (law), a decree that prohibits something, sometimes a form of censorship, being denied from entering or using the place/item
** Imperial ban (''Reichsacht''), a form of outlawry in the medieval Holy Roman ...
; or mecamylamine hydrochloride (
USAN
280px, "Samguk Sagi" Book 04. Silla's Records. In 512, Usan-guk(于山國)was Ulleungdo(鬱陵島)
Usan-guk, or the State of Usan, occupied Ulleung-do and the adjacent islands during the Korean Three Kingdoms period. According to th ...
); brand names Inversine, Vecamyl) is a
non-selective
In biochemistry and pharmacology, a ligand is a substance that forms a complex with a biomolecule to serve a biological purpose. The etymology stems from ''ligare'', which means 'to bind'. In protein-ligand binding, the ligand is usually a mole ...
,
non-competitive antagonist
An antagonist is a character in a story who is presented as the chief foe of the protagonist.
Etymology
The English word antagonist comes from the Greek ἀνταγωνιστής – ''antagonistēs'', "opponent, competitor, villain, enemy, ri ...
of the
nicotinic acetylcholine receptor
Nicotinic acetylcholine receptors, or nAChRs, are receptor polypeptides that respond to the neurotransmitter acetylcholine. Nicotinic receptors also respond to drugs such as the agonist nicotine. They are found in the central and peripheral ner ...
s (nAChRs) that was introduced in the 1950s as an
antihypertensive
Antihypertensives are a class of drugs that are used to treat hypertension (high blood pressure). Antihypertensive therapy seeks to prevent the complications of high blood pressure, such as stroke and myocardial infarction. Evidence suggests th ...
drug
A drug is any chemical substance that causes a change in an organism's physiology or psychology when consumed. Drugs are typically distinguished from food and substances that provide nutritional support. Consumption of drugs can be via inhala ...
.
In the
United States
The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country Continental United States, primarily located in North America. It consists of 50 U.S. state, states, a Washington, D.C., ...
, it was voluntarily withdrawn from the market in 2009 but was brought to market in 2013 as Vecamyl and eventually was marketed by
Turing Pharmaceuticals.
Chemically, mecamylamine is a secondary
aliphatic
In organic chemistry, hydrocarbons ( compounds composed solely of carbon and hydrogen) are divided into two classes: aromatic compounds and aliphatic compounds (; G. ''aleiphar'', fat, oil). Aliphatic compounds can be saturated, like hexane ...
amine
In chemistry, amines (, ) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (), wherein one or more hydrogen atoms have been replaced by a substituent ...
, with a pK
aH of 11.2
Pharmacology and clinical applications
Mecamylamine has been used as an orally-active
ganglionic blocker in treating
autonomic dysreflexia
Autonomic dysreflexia (AD) is a potential medical emergency classically characterized by uncontrolled hypertension and bradycardia, although tachycardia is known to commonly occur. AD occurs most often in individuals with spinal cord injuries wit ...
and
hypertension
Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high b ...
, but, like most ganglionic blockers, it is more often used now as a research tool.
Mecamylamine is also sometimes used as an
antiaddictive
Addiction is a neuropsychological disorder characterized by a persistent and intense urge to engage in certain behaviors, one of which is the usage of a drug, despite substantial harm and other negative consequences. Repetitive drug use of ...
drug to help people stop smoking tobacco,
and is now more widely used for this application than it is for lowering blood pressure. This effect is thought to be due to its blocking
α3β4 nicotinic receptors
Nicotinic acetylcholine receptors, or nAChRs, are receptor polypeptides that respond to the neurotransmitter acetylcholine. Nicotinic receptors also respond to drugs such as the agonist nicotine. They are found in the central and peripheral ner ...
in the brain. It has also been reported to bring about sustained relief from tics in
Tourette syndrome
Tourette syndrome or Tourette's syndrome (abbreviated as TS or Tourette's) is a common neurodevelopmental disorder that begins in childhood or adolescence. It is characterized by multiple movement (motor) tics and at least one vocal (phonic) ...
when a series of more usually used agents had failed.
In a recent double-blind, placebo-controlled Phase II trial in Indian patients with major depression, (''S'')-mecamylamine (TC-5214) appeared to have efficacy as an
augmentation therapy. This is the first substantive evidence that shows that compounds where the primary pharmacology is antagonism to neuronal nicotinic receptors will have antidepressant properties.
TC-5214 is currently in Phase III of clinical development as an add-on treatment and on stage II as a monotherapy treatment for major depression. The first results reported from the Phase III trials showed that TC-5214 failed to meet the primary goal and the trial did not replicate the effects that had been encouraging in the Phase II trial. Development is funded by Targacept and AstraZeneca. It did not produce meaningful, beneficial results on patients as measured by changes on the
Montgomery-Asberg Depression Rating Scale after eight weeks of treatment as compared with placebo.
(''S'')-(+)-Mecamylamine
dissociates more slowly from
α4β2 and
α3β4 receptors than does the (''R'')-(−)-
enantiomer
In chemistry, an enantiomer ( /ɪˈnænti.əmər, ɛ-, -oʊ-/ ''ih-NAN-tee-ə-mər''; from Ancient Greek ἐνάντιος ''(enántios)'' 'opposite', and μέρος ''(méros)'' 'part') – also called optical isomer, antipode, or optical anti ...
.
A large
SAR study of mecamylamine and its analogs was reported by a group from Merck in 1962.
Another, more recent
SAR study was undertaken by Suchocki et al.
A comprehensive review of the pharmacology of mecamylamine was published in 2001.
Toxicology
The for the HCl salt in mice: 21 mg/kg (i.v.); 37 mg/kg (i.p.); 96 mg/kg (p.o.).
History
Mecamylamine was brought to market by
Merck & Co. in the 1950s; in 1996 Merck sold the asset to
Layton Bioscience. In 2002, Targacept acquired it from Layton, intending to repurpose it for CNS conditions.
Targacept voluntarily withdrew mecamylamine from the market in 2009 for reasons not related to safety or efficacy. Manchester Pharmaceuticals brought the drug back to market in 2013.
Retrophin acquired Manchester in 2014 and after
Martin Shkreli was forced out of Retrophin, in 2014 his new company,
Turing Pharmaceuticals, acquired the rights to mecamylamine from Retrophin.
See also
*
Bupropion
Bupropion, sold under the brand names Wellbutrin and Zyban among others, is an atypical antidepressant primarily used to treat major depressive disorder and to support smoking cessation. It is also popular as an add-on medication in the cas ...
*
Scopolamine
Scopolamine, also known as hyoscine, or Devil's Breath, is a natural or synthetically produced tropane alkaloid and anticholinergic drug that is formally used as a medication for treating motion sickness and postoperative nausea and vomi ...
References
{{Nicotinic acetylcholine receptor modulators
Amines
Nicotinic antagonists
Withdrawn drugs
Bicyclic compounds