右旋芬氟拉明和去甲右旋芬氟拉明引起的食欲减退并不需要增加下丘脑5-羟色胺的释放。

d-Fenfluramine and d-norfenfluramine hypophagias do not require increased hypothalamic 5-hydroxytryptamine release.

作者信息

Oluyomi A O, Gibson E L, Barnfield A M, Curzon G

机构信息

Department of Neurochemistry, Institute of Neurology, London, UK.

出版信息

Eur J Pharmacol. 1994 Oct 13;264(1):111-5. doi: 10.1016/0014-2999(94)90646-7.

DOI:10.1016/0014-2999(94)90646-7

PMID:7828639

Abstract

d-Fenfluramine (2.5 mg/kg i.p.) caused marked hypophagia in food-deprived rats and significantly increased medial hypothalamic extracellular 5-hydroxytryptamine (5-HT) as indicated by in vivo microdialysis. When the drug was given after the 5-HT synthesis inhibitor p-chlorophenylalanine (150 mg/kg per day x 3) the hypophagic response was unimpaired but dialysate 5-HT concentration no longer rose. The d-fenfluramine metabolite d-norfenfluramine (1.5 mg/kg i.p.) caused slightly greater hypophagia than the parent drug and completely blocked feeding in animals pretreated with p-chlorophenylalanine, but dialysate 5-HT was increased in neither circumstance. The results provide evidence against mediation of the hypophagic effects of d-fenfluramine and d-norfenfluramine by increased availability of 5-HT to receptors.

摘要

右旋芬氟拉明（腹腔注射2.5毫克/千克）可使饥饿的大鼠出现明显的摄食减少，体内微透析结果表明，其可显著提高下丘脑内侧细胞外5-羟色胺（5-HT）的水平。当在给予5-HT合成抑制剂对氯苯丙氨酸（每天150毫克/千克，共3天）后再给予该药物时，摄食减少反应未受影响，但透析液中5-HT浓度不再升高。右旋芬氟拉明的代谢产物去甲右旋芬氟拉明（腹腔注射1.5毫克/千克）引起的摄食减少比母体药物略大，并且完全阻断了用对氯苯丙氨酸预处理动物的进食，但在这两种情况下透析液中的5-HT均未增加。这些结果提供了证据，反对通过增加5-HT与受体的结合来介导右旋芬氟拉明和去甲右旋芬氟拉明的摄食减少作用。