Pharmacodynamics and pharmacokinetics of AHR-11748, a new antiepileptic agent, in rodents.
AHR-11748, the desmethyl metabolite of fluzinamide (an effective antiepileptic), was active in preventing maximal seizures induced in mice or rats by electroshock and threshold seizures induced in mice by Metrazol, bicuculline, and picrotoxin. The compound showed a profile of anticonvulsant activity similar to those of phenobarbital and valproic acid and different from those of phenytoin and ethosuximide. ED50s were less than those of valproic acid, but greater than those of phenobarbital. Analysis of plasma and whole brain homogenates of mice indicated that AHR-11748 has an apparent terminal half-life (t1/2, beta) of 1.0 h. The brain:plasma ratio of AHR-11748 was 3.4:1 from 0.5 h to 6 h.
Johnson
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DN
Department of Pharmacology, A.H. Robins Research Laboratories, Richmond, VA 23220.
Osman
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MA
Cheng
L K
LK
Swinyard
E A
EA
D000284:Administration, Oral; D000818:Animals; D000927:Anticonvulsants / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001384:Azetidines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001385:Azetines / Q000627:therapeutic use*; D004827:Epilepsy / Q000139:chemically induced / Q000188:drug therapy*; D005260:Female; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR
D000927:Anticonvulsants; D001384:Azetidines; D001385:Azetines; C064672:AHR 11748