Evidence for involvement of the astrocytic benzodiazepine receptor in the mechanism of action of convulsant and anticonvulsant drugs.
The anticonvulsant drugs carbamazepine, phenobarbital, trimethadione, valproic acid and ethosuximide at pharmacologically relevant concentrations inhibit [3H]diazepam binding to astrocytes in primary cultures but have much less effect on a corresponding preparation of neurons. Phenytoin as well as pentobarbital (which is not used chronically as an anticonvulsant) are equipotent in the two cell types. The convulsants picrotoxinin and pentylenetetrazol, the convulsant benzodiazepine RO 5-3663 and the two convulsant barbiturates DMBB and CHEB similarly inhibit diazepam binding to astrocytes but have little effect on neurons. On the basis of these findings it is suggested that these convulsants and anticonvulsants owe at least part of their effect to an interaction with the astrocytic benzodiazepine receptor, perhaps by interference with a calcium channel.
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001253:Astrocytes / Q000378:metabolism*; D001463:Barbiturates / Q000031:analogs & derivatives / Q000494:pharmacology; D001570:Benzodiazepinones / Q000494:pharmacology; D001921:Brain / Q000378:metabolism*; D002220:Carbamazepine / Q000494:pharmacology; D002478:Cells, Cultured; D003292:Convulsants / Q000494:pharmacology*; D003975:Diazepam / Q000378:metabolism; D005013:Ethosuximide / Q000494:pharmacology; D051379:Mice; D009474:Neurons / Q000378:metabolism; D010433:Pentylenetetrazole / Q000494:pharmacology; D010634:Phenobarbital / Q000494:pharmacology; D010852:Picrotoxin / Q000031:analogs & derivatives / Q000494:pharmacology; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*; D054830:Sesterterpenes; D014293:Trimethadione / Q000494:pharmacology; D014635:Valproic Acid / Q000494:pharmacology
D000927:Anticonvulsants; D001463:Barbiturates; D001570:Benzodiazepinones; D002220:Carbamazepine; D003292:Convulsants; D003975:Diazepam; D005013:Ethosuximide; D010433:Pentylenetetrazole; D010634:Phenobarbital; D010852:Picrotoxin; D011963:Receptors, GABA-A; D054830:Sesterterpenes; D014293:Trimethadione; D014635:Valproic Acid; C024321:5-(2-cyclohexylidene-ethyl)-5-ethylbarbiturate; C056763:5-ethyl-5-(1,3-dimethylbutyl)-5-barbituric acid; C022193:Ro 5-3663; C022961:picrotoxinin