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首页> 外文期刊>Pharmacology, Biochemistry and Behavior >Discriminative stimulus effects of mecamylamine and nicotine in rhesus monkeys: Central and peripheral mechanisms
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Discriminative stimulus effects of mecamylamine and nicotine in rhesus monkeys: Central and peripheral mechanisms

机译：麦考胺和尼古丁在恒河猴中的鉴别刺激作用：中央和外周机制

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摘要

Mecamylamine is a non-competitive nicotinic acetylcholine receptor (nAChR) antagonist that has been prescribed for hypertension and as an off-label smoking cessation aid. Here, we examined pharmacological mechanisms underlying the interoceptive effects (i.e., discriminative stimulus effects) of mecamylamine (5.6 mg/kg s.c.) and compared the effects of nAChR antagonists in this discrimination assay to their capacity to block a nicotine discriminative stimulus (1.78 mg/kg s.c.) in rhesus monkeys. Central (pempidine) and peripherally restricted nAChR antagonists (pentolinium and chlorisondamine) dose-dependently substituted for the mecamylamine discriminative stimulus in the following rank order potency (pentolinium > pempidine > chlorisondamine > mecamylamine). In contrast, at equieffective doses based on substitution for mecamylamine, only mecamylamine antagonized the discriminative stimulus effects of nicotine, i.e., pentolinium, chlorisondamine, and pempidine did not. NMDA receptor antagonists produced dose-dependent substitution for mecamylamine with the following rank order potency (MK-801 > phencyclidine > ketamine). In contrast, behaviorally active doses of smoking cessation aids including nAChR agonists (nicotine, varenicline, and cytisine), the smoking cessation aid and antidepressant bupropion, and the benzodiazepine midazolam did not substitute for the discriminative stimulus effects of mecamylamine. These data suggest that peripheral nAChRs and NMDA receptors may contribute to the interoceptive stimulus effects produced by mecamylamine. Based on the current results, the therapeutic use of mecamylamine (i.e., for smoking or to alleviate green tobacco sickness) should be weighed against the potential for mecamylamine to produce interoceptive effects that overlap with another class of abused drugs (i.e., NMDA receptor agonists).
机译：Mecamylamine是一种非竞争性的烟酰乙酰胆碱受体（NACHR）拮抗剂，其被规定的高血压和作为非标签吸烟助性助剂。在此，我们检查了咪酰胺（即5.6mg / kg sc）的中断效应（即，鉴别刺激效应）的药理学机制，并比较了NACHR拮抗剂在这种辨别测定中的影响，以阻断尼古丁歧视性刺激的能力（1.78mg / kg sc）在恒河猴猴子。中央（Pempidine）和外周限制的NACHR拮抗剂（戊烯醇和氯胺胺）剂量依赖于以下等级顺序效力（戊烯鎓> Pempidine>氯丹尼胺> MeCamylamine）中的咪酰胺鉴别刺激。相反，在基于替代咪酰胺的替代剂的抵抗，仅咪酰胺拮抗尼古丁，即戊烯醇，氯胺和Pempidine的鉴别刺激作用。 NMDA受体拮抗剂用以下等级效力（MK-801> Phenyclidine>氯胺酮产生了对MeCamylamine的剂量依赖性取代。相比之下，行为活性剂量的吸烟戒烟艾滋病，包括Nachr激动剂（尼古丁，varenicline和cytisine），吸烟戒烟和抗抑郁的小菌，以及苯并二氮卓咪达唑仑不替代咪酰胺的鉴别刺激作用。这些数据表明外周NACHR和NMDA受体可能有助于MeCamylamine产生的中断刺激效果。基于当前结果，应称重咪酰胺（即吸烟或吸烟或缓解绿色烟草疾病）的治疗用途，以抵御咪酰胺的可能性，以产生与另一种滥用药物重叠的间歇性效果（即，NMDA受体激动剂） 。

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