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Related Experiment Videos

Nicotine-mecamylamine interactions.

S Zevin1, P Jacob, N L Benowitz

  • 1Division of Clinical Pharmacology and Experimental Therapeutics, Medical Service, San Francisco General Hospital Medical Center, University of California, USA.

Clinical Pharmacology and Therapeutics
|August 17, 2000
PubMed
Summary
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Mecamylamine, when combined with nicotine, may aid smoking cessation by altering nicotine distribution. This study found mecamylamine reduces nicotine

Area of Science:

  • Pharmacology
  • Clinical Pharmacology
  • Nicotinic Receptor Antagonism

Background:

  • Mecamylamine, a nicotinic cholinergic receptor blocker, is investigated as a potential adjunct to nicotine therapy for smoking cessation.
  • Understanding the pharmacokinetic and pharmacodynamic interactions between mecamylamine and nicotine is crucial for optimizing this combination therapy.

Purpose of the Study:

  • To characterize the pharmacokinetic and pharmacodynamic interactions between transdermal mecamylamine and intravenous nicotine in cigarette smokers.
  • To evaluate the impact of mecamylamine on nicotine and cotinine disposition kinetics.
  • To assess the effects of mecamylamine on nicotine-induced cardiovascular and catecholamine responses.

Main Methods:

  • A randomized, placebo-controlled study involving 12 cigarette smokers receiving transdermal mecamylamine or placebo for 7 days.

Related Experiment Videos

  • On day 5, subjects received an infusion of deuterium-labeled nicotine and cotinine, with disposition kinetics measured.
  • Cardiovascular and plasma catecholamine responses to nicotine were monitored, with half the subjects studied under alkaline urine conditions.

    • Main Results:

    • Mecamylamine concentrations were higher under alkaline urine conditions due to reduced renal clearance.
    • Mecamylamine did not significantly alter the clearance of nicotine or cotinine.
    • Mecamylamine significantly reduced nicotine's volume of distribution and inhibited its cardioacceleratory and epinephrine-releasing effects.

    Conclusions:

    • Mecamylamine has minimal impact on nicotine clearance, suggesting stable nicotine levels during transdermal nicotine therapy.
    • Reduced nicotine volume of distribution by mecamylamine may indicate decreased brain transport or receptor binding, contributing to CNS effect antagonism.
    • Mecamylamine may mitigate adverse cardiovascular effects associated with coadministered nicotine.