Mecamylamine – a nicotinic acetylcholine receptor antagonist with potential for the treatment of neuropsychiatric disorders

  title={Mecamylamine – a nicotinic acetylcholine receptor antagonist with potential for the treatment of neuropsychiatric disorders},
  author={Ingrid Bacher and Becky S. Wu and Douglas Ronald Shytle and Tony P. George},
  journal={Expert Opinion on Pharmacotherapy},
  pages={2709 - 2721}
Mecamylamine (Inversine®), the first orally available antihypertensive agent launched in the 1950s, is rarely used today for hypertension because of its widespread ganglionic side effects at antihypertensive doses (25 – 90 mg/day). However, more recent clinical studies suggest that mecamylamine is effective at much lower doses for blocking the central and peripheral effects of nicotine. Pharmacologically, mecamylamine has been well characterized as a nonselective and noncompetitive antagonist… 

Potential therapeutic uses of mecamylamine and its stereoisomers

Nicotinic acetylcholine receptors and depression: a review of the preclinical and clinical literature

Preclinical and clinical evidence suggests that drugs targeting nicotinic acetylcholine receptors (nAChRs) may represent an important new approach to the treatment of depression.

Au-delà des antidépresseurs sérotoninergiques... nouvelles stratégies pharmacologiques

Although mood disorders such as depression are better diagnosed, their treatment often remains unsatisfactory. Pharmacological treatments of depression mostly target the central monoaminergic

α6β2* and α4β2* Nicotinic Acetylcholine Receptors As Drug Targets for Parkinson's Disease

NAChRs are reviewed with particular emphasis on the subtypes that contribute to basal ganglia function and accumulation evidence suggests that drugs targeting α6β2* and α4 β2* nAChR may prove useful in the management of Parkinson's disease.

The Nicotinic Acetylcholine Receptor as a Target for Antidepressant Drug Development

Preliminary results in this area constitute a compelling argument for further evaluation of the nAChR as a target for future antidepressant drug development.

Is the Antidepressant Activity of Selective Serotonin Reuptake Inhibitors Mediated by Nicotinic Acetylcholine Receptors?

Studies on dorsal raphe nucleus serotoninergic neurons support the concept that SSRI-induced nAChR inhibition decreases the glutamatergic hyperstimulation observed in stress conditions, which compensates the excessive 5-HT overflow in these neurons and, consequently, ameliorates depression symptoms.

Allosteric modulation and potential therapeutic applications of heteromeric nicotinic acetylcholine receptors

This review will discuss the primary lead compounds identified to date that allosterically potentiate or inhibit heteromeric nAChRs, including α4β2 and α3β4 subtypes, with a focus on the current understanding of these structural and functional relationships.



Mecamylamine (Inversine®): an old antihypertensive with new research directions

Low-dose mecamylamine therapy might reduce blood pressure variability and atherogenetic lipid profile in smokers and be an important research tool in the field of hypertension research, particularly in recalcitrant smokers with mild to moderate hypertension.

Nicotinic acetylcholine receptors as targets for antidepressants

Preliminary evidence is presented suggesting that the potent, centrally acting nAChR antagonist, mecamylamine, which is devoid of monoamine reuptake inhibition, may reduce symptoms of depression and mood instability in patients with comorbid depression and bipolar disorder.

Nicotinic Antagonist Augmentation of Selective Serotonin Reuptake Inhibitor-Refractory Major Depressive Disorder: A Preliminary Study

Preliminary findings suggest that the nicotinic acetylcholine receptor antagonist, MEC, may have utility as an augmentation strategy for patients with SSRI-refractory MDD.

Nicotinic cholinergic antagonists: a novel approach for the treatment of autism.

Nicotine and nicotinic receptor involvement in neuropsychiatric disorders.

This manuscript reviews data, both experimental and clinical, relating to the role of nicotine and/or nicotinic receptor function in a variety of neuropsychiatric disorders with the perspective of developing appropriate targets for therapeutic drug development.

Analysis of mecamylamine stereoisomers on human nicotinic receptor subtypes.

It is suggested that in chronic (i.e., therapeutic) application, S-(+)-mecamylamine might be preferable to R-(-)-micylamine in terms of equilibrium inactivation of neuronal receptors with decreased side effects associated with muscle-type receptors.

Age-Related Effects of the Nicotinic Antagonist Mecamylamine on Cognition and Behavior

The results indicate that acute blockade of nicotinic receptor function can produce measurable and significant cognitive impairment similar to some deficits seen in dementing illnesses, and that there is an age-related increase in sensitivity to Nicotinic blockade.

Exploiting Nicotinic Receptor Mechanisms for the Treatment of Schizophrenia and Depression

Smoking rates are higher in persons with schizophrenia (SZ; 58%–88%) and major depressive disorder (MDD; 40%–60%) compared to the U.S. general population (∼23%). Nicotinic acetylcholine receptors

Neuropsychological deficits in nonsmokers with schizophrenia: Effects of a nicotinic antagonist