Palmer G C, Stagnitto M L, Garske G E, Napier J J, Harris E W, Kaiser F C, Griffith R C, Woodhead J H, White H S, Wolf H H
Fisons Pharmaceuticals, Divisional Research and Development, Rochester, New York, USA.
J Pharmacol Exp Ther. 1995 Jun;273(3):1023-31.
2-Amino-N-(1,2-diphenylethyl)-acetamide-hydrochloride (FPL 13950) was profiled preclinically in rodents for efficacy against convulsions, as well as for acute safety/behavioral observations. FPL 13950 exhibited good oral efficacy and duration of action with respect to prevention of seizures elicited by maximal electroshock-shock in both rats and mice. Tolerance to protection against maximal electroshock and hexobarbital-induced sleep-time was not evident after subchronic drug administration. FPL 13950 also prevented convulsions/mortality in mice after i.v. dosing with N-methyl-D, L-aspartate, however, it was ineffective against other types of chemically induced convulsions, as well as bicorneal kindling. High oral doses produced neural impairment in both mice and rats and hyperactivity in rats. Sequential administration of yet higher doses elicited tonic/clonic convulsions culminating in death. During i.v. infusion of metrazol in mice, high i.p. doses of FPL 13950 shortened the latency to first twitch and clonus. No increase in the startle response or phencyclidine-like behavior was evident after oral dosing in rats.
2-氨基-N-(1,2-二苯乙基)乙酰胺盐酸盐(FPL 13950)在啮齿动物中进行了临床前研究,以评估其抗惊厥疗效以及急性安全性/行为观察。FPL 13950在预防大鼠和小鼠最大电休克诱发的癫痫发作方面表现出良好的口服疗效和作用持续时间。亚慢性给药后,未观察到对最大电休克和戊巴比妥诱导睡眠时间的保护耐受性。FPL 13950静脉注射N-甲基-D,L-天冬氨酸后也可预防小鼠惊厥/死亡,然而,它对其他类型的化学诱导惊厥以及双角膜点燃无效。高口服剂量在小鼠和大鼠中均产生神经损伤,在大鼠中产生多动。连续给予更高剂量会引发强直性/阵挛性惊厥,最终导致死亡。在小鼠静脉注射戊四氮期间,高腹腔注射剂量的FPL 13950缩短了首次抽搐和阵挛的潜伏期。大鼠口服给药后,惊吓反应或苯环己哌啶样行为没有明显增加。