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首页> 外文期刊>Pharmacology, Biochemistry and Behavior >Lack of effect of 5HT(3) antagonist in mediating subjective and behavioral responses to cotinine.
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Lack of effect of 5HT(3) antagonist in mediating subjective and behavioral responses to cotinine.

机译：缺乏5HT（3）拮抗剂对介导可替宁的主观和行为反应的影响。

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Previous studies have shown that cotinine, a metabolite of nicotine, may antagonize some of the therapeutic effects of nicotine. The mechanisms underlying cotinine's effects are unclear, but cotinine has been observed to increase serotonin levels in the brain. Thus, it is possible that blocking serotonin effects may antagonize the actions of cotinine, thereby reducing its impact on responses to nicotine. This study determined whether granisetron, a 5HT(3) receptor antagonist, would enhance the efficacy of the nicotine patch. Subjects were randomly assigned to one of the three granisetron conditions (N=43 for 2 mg/day; N=43 for 1 mg/day; N=42 for 0 mg/day) and asked to take the assigned medication daily during 15 days of tobacco abstinence. Because we were interested in interactions between cotinine and serotonin, all groups were also treated with a 21-mg nicotine patch. Assessments of withdrawal symptoms were made for 1 week during baseline smoking and several times during the experimental period. There was a near but nonsignificant difference among groups on a measure of tobacco withdrawal and no significant differences on global measures of drug effects or physiological measures. The data do not strongly support the hypothesis that 5HT(3) agonism is the mechanism by which cotinine offsets the effects of nicotine.
机译：先前的研究表明，可替宁是尼古丁的一种代谢产物，可能拮抗尼古丁的某些治疗作用。可替宁作用的潜在机制尚不清楚，但已观察到可替宁会增加大脑中5-羟色胺的水平。因此，阻断5-羟色胺的作用可能拮抗可替宁的作用，从而减少其对尼古丁反应的影响。这项研究确定了Granisetron（一种5HT（3）受体拮抗剂）是否会增强尼古丁贴片的功效。受试者被随机分配到三种Granisetron状况之一（N = 43，每天2 mg; N = 43，每天1 mg; N = 42，每天0 mg），并要求他们在15天内每天服用指定的药物戒烟。因为我们对可替宁和血清素之间的相互作用感兴趣，所以所有组也都接受了21 mg尼古丁贴剂的治疗。在基线吸烟期间评估戒断症状持续1周，在实验期间评估几次。各组之间在戒烟量方面几乎没有差异，但在整体药物效果或生理指标上没有显着差异。数据没有强烈支持5HT（3）激动是可替宁抵消尼古丁影响的机制的假设。

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