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• W2000665240 abstract "Studies conducted by Fisons Pharmaceuticals and the Antiepileptic Drug Development Program (ADD Program) of the Epilepsy Branch (NINDS, NIH) revealed that ‘remacemide’ (FPL 12924, formerly PR 934-423) was effective orally in the prevention of maximal electroshock seizures (MES) in rats. In this context (−)stereoisomer (FPL 14145) was of equal potency to the racemate (remacemide), while the (+) stereoisomer (FPL 14144) was 54% less potent. With respect to neurotoxicity, remacemide and its enantiomers possessed more favorable therapeutic indices than phenobarbital and valproate and less favorable indices than phenytoin and carbamazepine. The duration of protection of rats in the MES test at the ED50 or 3 × ED50 of remacemide and the (+)isomer was better or on par with the best reference compounds, phenytoin and phenobarbital. After subchronic administration of either the ED50 or the ED97 of remacemide, no tolerance developed in the hexobarbital sleep test, however, the activities of 3 hepatic microsomal enzymes were elevated. In naive rats high doses of remacemide or its (−)isomer and low doses of phenobarbital caused an increase in spontaneous motor activity. Alternatively, motor activity was depressed subsequent to high doses of phenobarbital and phenytoin. Remacemide was inactive against pentylenetetrazol and ‘kindling’ seizures. It was without effect in 5 electrophysiological tests (evoked responses, recurrent inhibition, longterm potentiation, penicillin-induced discharge rate and veratridine-induced depolarization) employing the in vitro hippocampal slice technique. Moreover, remacemide failed to demonstrate potent binding in vitro to neuronal l-glutamate, γ-amino-butyrate A, adenosine A1, benzodiazepine, N-methyl-d-aspartate (strychnine-insensitive glycine and ion channel subsites) or muscarinic receptors. In conclusion, remaoemide specifically prevents seizures elicited by MES, an action predicting utility in patients with generalized tonic/clonic convulsions." @default.
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• W2000665240 date "1991-09-01" @default.
• W2000665240 modified "2023-09-27" @default.
• W2000665240 title "Preclinical profile of the anticonvulsant remacemide and its enantiomers in the rat" @default.
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• W2000665240 doi "https://doi.org/10.1016/0920-1211(91)90050-p" @default.
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