From Fenfluramine Racemate to d‐Fenfluramine
From Fenfluramine Racemate to d‐Fenfluramine
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从芬氟拉明外消旋体到 d-芬氟拉明
DOI：
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发表时间：
1987
期刊：
影响因子：
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通讯作者：
R. Samanin
中科院分区：
文献类型：
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作者：
S. Garattini;T. Mennini;R. Samanin
利用各种单胺配体结合大鼠脑膜和突触体制剂研究单胺摄取和释放的实验表明，d-芬氟拉明在抑制5-HT摄取方面比l异构体更有效，而d-去甲芬氟拉明优先从利血平不敏感的腔室释放5-HT。完整动物脑单胺代谢研究表明，相对低剂量的芬氟拉明d和l异构体分别对脑5-羟色胺和儿茶酚胺具有特异性作用。基于美高林和利坦色林取代5-HT2结合大鼠脑膜和拮抗d-芬氟拉明厌食症的能力不同，有证据表明d-芬氟拉明优先利用大鼠脑中的5-HT1位点引起该动物的厌食症。最后，描述了与大鼠脑膜结合的高亲和力[3H]d-芬氟拉明的特征、区域分布和药理学特征。这种结合似乎不同于5-HT摄取位点（[3H]丙咪嗪结合）和5-HT受体，并且与大鼠脑内源性5-HT水平没有区域关系。然而，它被一些使用5-羟色胺的药物优先取代，导致大鼠厌食症，这可能与5-羟色胺参与喂养控制的机制有关。
: Experiments using the binding of various ligands for monoamines to rat brain membranes and synaptosomal preparations for studying monoamine uptake and release have shown that d-fenfluramine is more potent than the l isomer in inhibiting 5-HT uptake, whereas d-norfenfluramine preferentially releases 5-HT from a reserpine-insensitive compartment. Studies on brain monoamine metabolism in intact animals have shown that the d and l isomers of fenfluramine at relatively low doses have a specific action on brain 5-HT and catecholamines, respectively. Based on the different ability of metergoline and ritanserin to displace 5-HT2 binding to rat brain membranes and to antagonize d-fenfluramine's anorexia, evidence has been provided that d-fenfluramine preferentially uses 5-HT1 sites in the rat brain to cause anorexia in this animal species. Finally, characteristics, regional distribution, and pharmacological characterization of a high-affinity [3H]d-fenfluramine binding to rat brain membranes have been described. This binding appears to be different from 5-HT uptake sites ([3H]imipramine binding) and 5-HT receptors and is not regionally related to the endogenous levels of 5-HT in the rat brain. It is, however, preferentially displaced by some agents using 5-HT to cause anorexia in rats, raising the possibility that it is somewhat related to 5-HT mechanisms involved in feeding control.