The temporal dimensions of anticonvulsant action of some newer benzodiazepines against metrazol induced seizures in mice and rats.
In a time-distribution study, the anticonvulsant effects of four benzodiazepine compounds were compared with those of three standard antiepileptics against metrazol-induced seizures in mice and rats. Ethosuximide and trimethadione had the shortest duration of action in mice, but protected the rats up to 6 hr. Phenobarbitone, diazepam, flurazepam and nitrazepam protected the mice up to 12 hr, but the rats were effectively protected only up to 3-4 hr. Clonazepam, the most potent and effective agent, protected the mice from clonic-tonic seizures up to 18-20 hr and the rats up to 6-7 hr. Comparison of the PD50 from clonic seizure at the peak-effect hours revealed that the benzodiazepines were 16 to 96 times more potent than phenobarbitone on a molar basis, while phenobarbitone itself was 12 to 26 times more potent than ethosuximide and trimethadione. Tonic seizures and mortality were largely suppressed by all drugs until 18-20 hr in mice and 6-7 hr in rats. Seizure latency and mortality patterns varied from drug to drug but not in a dose-dependent manner.
D000818:Animals; D001569:Benzodiazepines / Q000627:therapeutic use*; D002998:Clonazepam / Q000627:therapeutic use; D003975:Diazepam / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical; D005013:Ethosuximide / Q000627:therapeutic use; D005260:Female; D005479:Flurazepam / Q000627:therapeutic use; D008297:Male; D051379:Mice; D009567:Nitrazepam / Q000627:therapeutic use; D010433:Pentylenetetrazole; D010634:Phenobarbital / Q000627:therapeutic use; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy*; D014293:Trimethadione / Q000627:therapeutic use
D001569:Benzodiazepines; D002998:Clonazepam; D005013:Ethosuximide; D009567:Nitrazepam; D005479:Flurazepam; D003975:Diazepam; D014293:Trimethadione; D010433:Pentylenetetrazole; D010634:Phenobarbital