Evaluation of anticonvulsant drugs in gerbils with reflex epilepsy.
In more than 98% of randomly bred gerbils epileptic seizures could be evoked by blowing at the animals with compressed air (5 bars for 10 s). In contrast, only few animals showed seizures in response to environmental stimuli (e.g., new cage) and handling. Thus, administration of drugs was possible without precipitating seizures. The severity of the seizures was rated on a seven-point scale. Seizure severity increased with age and reached its maximum at about 7 months. Comparison of pharmacokinetics of common antiepileptic drugs showed that these drugs, except phenobarbital, were rapidly eliminated by the gerbil which, in this respect, resembled the mouse. For determination of anticonvulsant ED50S of antiepileptic drugs in gerbils there was differentiated between "minor" seizures (grade 1-2; myoclonic seizures) and "major" seizures (grade 3-5; generalized clonic-tonic seizures). Phenobarbital, phenytoin and carbamazepine were more potent against major seizures than against minor seizures, whereas the reverse situation was obtained with diazepam, valproic acid and ethosuximide. The relative activity of the different antiepileptic drugs against minor and major seizures in gerbils corresponded to the respective activity in traditional mouse models of petit mal and grand mal epilepsy. In further experiments, a series of GABAmimetic drugs was tested, namely, compounds that selectively increase gamma-aminobutyric acid (GABA)-mediated neuronal inhibition in the brain.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D004827:Epilepsy / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D005849:Gerbillinae; D007700:Kinetics; D008297:Male; D051379:Mice; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D000927:Anticonvulsants; D005680:gamma-Aminobutyric Acid