Mecamylamine: New therapeutic uses and toxicity/risk profile

Background: Mecamylamine hydrochloride was initially developed for its ganglion-blocking activity and has been marketed as an antihypertensive agent in the United States for > 40 years. Several other potential therapeutic applications are being investigated, most of them focusing on the drug's ability to cross the blood-brain barrier and selectively antagonize neuronal nicotinic acetylcholine receptors. This central activity of mecamylamine is demonstrable at much lower doses than the effective antihypertensive dose, thus avoiding many of the bothersome side effects associated with the drug's inhibition of parasympathetic activity. Objective: Because investigations are being conducted in new patient populations, including pediatric patients, an update of the toxicity/risk profile of mecamylamine is timely. This review describes nonclinical and clinical data pertaining to the pharmacology, toxicity, and tolerability of mecamylamine, including some previously unpublished toxicology and clinical pharmacokinetics data. Potential new therapeutic applications are discussed, including the use of mecamylamine in treating autonomic dysreflexia; dependencies on nicotine, cocaine, and other substances of abuse: Tourette's syndrome; and Other neuropsychiatric disorders. Methods: Information for this review of mecamylamine was identified through a search of MEDLINE (R) from 1966 to the present, as well as from the master files of Merck & Co. Inc, the drug's original manufacturer, and Layton BioScience. Inc. its present manufacturer. Conclusions: The available data concerning potential new applications of mecamylamine, although sparse, suggest that the drug's toxicity/risk profile may be much improved at lower doses.