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Anticonvulsant efficacy/safety properties of 2-amino-N-(1,2- diphenylethyl)acetamide hydrochloride

GC Palmer, ML Stagnitto, GE Garske, JJ Napier, EW Harris, FC Kaiser, RC Griffith, JH Woodhead, HS White and HH Wolf

Fisons Pharmaceuticals, Divisional Research and Development, Rochester, New York, USA.

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.

Volume 273, Issue 3, pp. 1023-1031, 06/01/1995
Copyright © 1995 by American Society for Pharmacology and Experimental Therapeutics




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Copyright © 1995 by the American Society for Pharmacology and Experimental Therapeutics.