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.
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Behav Pharmacol
November 2002
Department of Pharmacology and Toxicology, Medical College of Virginia Commonwealth University, Richmond, Virginia 23298-0613, USA.
Low-affinity channel-blocking -methyl-D-aspartate (NMDA) antagonists have been of interest for clinical development because they are purported to produce few phencyclidine (PCP)-like side-effects, particularly at therapeutic doses. In the current study, two low-affinity NMDA channel blockers, AR-R 13950AA and AR-R 16283AA, were evaluated for NMDA antagonist-associated behavioral effects. The drugs were tested in rats and rhesus monkeys trained to discriminate PCP from saline, using a standard two-lever drug discrimination paradigm, under a fixed-ratio (FR) schedule of food reinforcement.
View Article and Find Full Text PDFJ Pharmacol Exp Ther
August 1995
Astra Research Corporation, Rochester, New York, USA.
2-Amino-N-(1,2-diphenylethyl)-acetamide hydrochloride (FPL 13950) has been demonstrated to have good anticonvulsant efficacy and a relative lack of acute side effects in rodents. Similar in structure to remacemide hydrochloride, it was also shown to possess weak potency as an uncompetitive antagonist of N-methyl-D-aspartic acid (NMDA) receptors. In our study FPL 13950 was profiled preclinically as a potential neuroprotective agent with respect to lengthening the survival time of rodents exposed to hypoxia, as well as for ability to protect the vulnerable CA1 pyramidal neurons of the rat and dog from the consequences of global ischemia.
View Article and Find Full Text PDFJ Pharmacol Exp Ther
June 1995
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.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!