Tekes K, Tóthfalusi L, Malomvölgyi B, Hermán F, Magyar K
Department of Pharmacodynamics, Semmelweis University of Medicine, Budapest, Hungary.
Pol J Pharmacol Pharm. 1987 Mar-Apr;39(2):203-11.
We studied the mode of action of N-benzyl-piperazine-picolinylfumarate (EGYT-475) and of its metabolite N-benzyl-piperazine (EGYT-2760) in CFY rats. It was found that EGYT-475 had no uptake-inhibitory effect but EGYT-2760 inhibited the high-affinity uptake of 3H-noradrenaline, 3H-dopamine and especially that of 3H-serotonin both in vitro and ex vivo. Neither of the two compounds changed the serotonin turnover. Only EGYT-2760 evoked hyperthermia in rats at a high ambient temperature (28 degrees C). This effect was abolished by cyproheptadine but not by amitriptyline. EGYT-2760 antagonized serotonin-induced contractions of the stomach fundus but it was inactive in inhibiting the serotonin-induced platelet aggregation. Our results suggest that EGYT-2760, an active metabolite of EGYT-475, has a central serotoninomimetic action which involves 5-HT uptake-inhibition and 5-HT1 receptor agonistic effect.
我们研究了富马酸N-苄基-哌嗪-吡啶基酯（EGYT-475）及其代谢产物N-苄基-哌嗪（EGYT-2760）在CFY大鼠体内的作用方式。结果发现，EGYT-475没有摄取抑制作用，但EGYT-2760在体外和体内均能抑制3H-去甲肾上腺素、3H-多巴胺尤其是3H-5-羟色胺的高亲和力摄取。这两种化合物均未改变5-羟色胺的周转率。只有EGYT-2760在高环境温度（28摄氏度）下能引起大鼠体温过高。该效应可被赛庚啶消除，但不能被阿米替林消除。EGYT-2760能拮抗5-羟色胺诱导的胃底收缩，但对抑制5-羟色胺诱导的血小板聚集无活性。我们的结果表明，EGYT-475的活性代谢产物EGYT-2760具有中枢5-羟色胺模拟作用，涉及5-羟色胺摄取抑制和5-HT1受体激动效应。
