An analysis of the in vivo interactions between chemical convulsants and anticonvulsants.
The interactions between pentylenetetrazol (PTZ), picrotoxin (PIC), or bicuculline (BIC) and diazepam, phenobarbital, or valproate were subjected to Schild plot analysis. Log dose-probit response curves for minimal clonic seizures were determined for three chemical convulsants in the absence and in the presence of various concentrations of three anticonvulsants. The calculated median convulsant doses were subjected to Schild plot analysis and the pA2 values determined. A comparison of the pA2 values for the various convulsant/anticonvulsant combinations suggested the following conclusions: (i) the sequence of events leading to minimal clonic seizures evoked by PTZ or PIC involves a common receptor, (ii) BIC acts through a different receptor, and (iii) Schild plot analysis of the antagonism between convulsant and anticonvulsant is in agreement with their antagonism in vitro studies. Thus, Schild plot analysis can be useful in the evaluation of anticonvulsant activity in vivo and may offer some insight into the potential clinical usefulness of anticonvulsant substances.
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001640:Bicuculline / Q000494:pharmacology; D003292:Convulsants / Q000494:pharmacology*; D003975:Diazepam / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D051379:Mice; D010433:Pentylenetetrazole / Q000494:pharmacology; D010634:Phenobarbital / Q000494:pharmacology; D010852:Picrotoxin / Q000494:pharmacology; D014635:Valproic Acid / Q000494:pharmacology
D000927:Anticonvulsants; D001640:Bicuculline; D003292:Convulsants; D003975:Diazepam; D010433:Pentylenetetrazole; D010634:Phenobarbital; D010852:Picrotoxin; D014635:Valproic Acid