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辛罗米德在猴子模型中的代谢产物:胃内给药与癫痫控制。

Cinromide's metabolite in monkey model: gastric administration and seizure control.

作者信息

Lockard J S, Levy R H, DuCharme L L, Congdon W C

出版信息

Epilepsia. 1980 Apr;21(2):177-82. doi: 10.1111/j.1528-1157.1980.tb04059.x.

Abstract

In a previous study (Lockard et al., 1979) Cinromide (3 bromo-N-ethylcinnamamide), an experimental anticonvulsant (Burroughs-Wellcome Pharmaceutical Co.), was given a preliminary evaluation. Since that research was concerned primarily with EEG paroxysms, the present study was conducted to address drug efficacy in terms of clinical seizures. Cinromide's major metabolite (3-bromocinnamamide, BC) was the main focus. Eight alumina-gel monkeys were given by gastric bolus every 6 hr for 10 days (Phase I) either the solvent alone (Tween 80), Cinromide (BEC), or its synthetic metabolite (SBC). Subsequently (Phase II), four animals were given BEC or SBC by chronic gastric infusion for 20 days. In both phases Cinromide's metabolite (either via BEC or especially SBC) was effective in half of the animals in reducing seizure frequency and/or duration at plasma levels above 5 mcg/m. The data suggest that the drug's efficacy is individually specific. Another species of Cinromide metabolism, 3-bromocinnamic acid, is also discussed.

摘要

在之前的一项研究中(洛卡德等人,1979年),对一种实验性抗惊厥药物辛罗米特(3-溴-N-乙基肉桂酰胺,由百时美施贵宝制药公司生产)进行了初步评估。由于之前的研究主要关注脑电图阵发性活动,因此本研究旨在探讨该药物在临床癫痫发作方面的疗效。辛罗米特的主要代谢产物(3-溴肉桂酰胺,BC)是主要研究对象。八只氧化铝凝胶猴每6小时经胃给予一次,持续10天(第一阶段),分别给予单独的溶剂(吐温80)、辛罗米特(BEC)或其合成代谢产物(SBC)。随后(第二阶段),四只动物经慢性胃内输注给予BEC或SBC,持续20天。在两个阶段中,辛罗米特的代谢产物(无论是通过BEC还是特别是SBC)在一半的动物中有效,当血浆水平高于5微克/毫升时可降低癫痫发作频率和/或持续时间。数据表明该药物的疗效具有个体特异性。还讨论了辛罗米特的另一种代谢产物3-溴肉桂酸。

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