Methamphetamine-like discriminative stimulus effects of bupropion and its two hydroxy metabolites in male rhesus monkeys.
作者： Matthew L. Banks , Douglas A. Smith , Bruce E. Blough
DOI: 10.1097/FBP.0000000000000224
关键词:
摘要: The dopamine transporter (DAT) inhibitor and nicotinic acetylcholine (nACh) receptor antagonist bupropion is being investigated as a candidate 'agonist' medication for methamphetamine addiction. In addition to its complex pharmacology, also has two distinct pharmacologically active metabolites. However, the mechanism by which produces methamphetamine-like effects remains unknown. aim of present study was determine role DAT inhibition, nACh antagonism, hydroxybupropion metabolites in discriminative stimulus rhesus monkeys. addition, varenicline, partial agonist at receptor, risperidone, antagonist, were tested controls. Monkeys (n=4) trained discriminate 0.18 mg/kg intramuscular from saline two-key food-reinforced discrimination procedure. potency time course determined all compounds. Bupropion, methylphenidate, 2S,3S-hydroxybupropion produced full, least 90%, effects. 2R,3R-Hydroxybupropion, mecamylamine, nicotine full effects, but drug more variable between Varenicline whereas risperidone did not. Overall, these results suggest inhibition major bupropion, although antagonism appeared, partially, contribute. Furthermore, contribution metabolite could not be completely ruled out.
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