Fuller R W, Snoddy H D
Lilly Research Laboratories, Eli Lilly & Co., Lilly Corporate Center, Indianapolis, IN 46285, U.S.A.
Neurochem Int. 1990;16(3):309-12. doi: 10.1016/0197-0186(90)90107-5.
The effects of two anorectic drugs, CM 57227 (4-amino-1-[6-chloropyrid-2-yl]piperidine) and CM 57373 (its 6-bromo analog), on brain serotonin metabolism in rats were studied. Both compounds dose-dependently decreased brain concentrations of 5-hydroxyindoleacetic acid (5-HIAA) for several hours while causing little or no change in brain concentrations of serotonin. Both compounds antagonized the depletion of brain serotonin by p-chloroamphetamine, an agent whose depletion requires the serotonin uptake carrier, with ED(50) values of about 7 mg/kg. The data suggest these compounds affect brain serotonin neurons primarily by inhibiting the membrane uptake carrier, which may be the mechanism by which they produce anorexia.
研究了两种食欲抑制剂CM 57227（4-氨基-1-[6-氯吡啶-2-基]哌啶）和CM 57373（其6-溴类似物）对大鼠脑血清素代谢的影响。两种化合物均能在数小时内剂量依赖性地降低脑内5-羟吲哚乙酸（5-HIAA）的浓度，而脑内血清素浓度几乎没有变化或无变化。两种化合物均能拮抗对氯苯丙胺引起的脑血清素耗竭，对氯苯丙胺的耗竭需要血清素摄取载体，其半数有效剂量（ED50）值约为7mg/kg。数据表明，这些化合物主要通过抑制膜摄取载体来影响脑血清素神经元，这可能是它们产生厌食作用的机制。
