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Nicotine and varenicline share discriminative stimulus properties and act through mecamylamine‐sensitive receptors in rhesus monkeys.
Author(s) -
Cunningham Colin Seamus,
McMahon Lance R
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.580.4
Subject(s) - varenicline , mecamylamine , nicotine , pharmacology , smoking cessation , agonist , nicotinic agonist , medicine , receptor , pathology
Varenicline is reported to be more effective than nicotine in promoting smoking cessation. To examine pharmacologic factors (i.e., site of action and efficacy at nicotine acetylcholine receptors) that could underlie differences in the clinical effectiveness of these smoking cessation pharmacotherapies, these and other drugs were studied in rhesus monkeys (n=3) discriminating nicotine (1.78 mg/kg, s.c.) from saline. Nicotine and varenicline (ED50 = 0.50 mg/kg and 0.56 mg/kg respectively) produced ≥91% nicotine‐lever responding. Cocaine produced a maximum of 50% nicotine‐lever responding; however, other drugs that act through non‐nicotine receptors (midazolam and ketamine) produced ≤4% nicotine‐lever responding. The nicotine antagonist mecamylamine dose‐dependently antagonized the effects of nicotine and varenicline. These data show that the nicotine discrimination assay is mediated by nicotine receptor agonism and, to some extent, monoamine agonism. The qualitatively similar effects of varenicline and nicotine and the similar antagonism of these agonists suggest that common, mecamylamine‐sensitive receptors mediate the effects of both agonists. Under these conditions in vivo, there is no evidence that nicotine and varenicline differ in their nicotine agonist efficacy. Studies were funded by USPHS grant DA25267.