Rimcazole, a sigma receptor ligand, and the anticonvulsive action of conventional antiepileptic drugs.
Rimcazole (a selective sigma receptor antagonist) at 5 and 10 mg/kg, 30 min before the test, lowered the electroconvulsive threshold, being ineffective at 2.5 mg/kg. Rimcazole (2.5 and 5 mg/kg) enhanced the protective activity of phenobarbital and valproate, but not that of carbamazepine and diphenylhydantoin against maximal electroshock. The effect of rimcazole upon the electroconvulsive threshold was reversed by haloperidol (0.5 mg/kg), but the rimcazole-induced potentiation of the anticonvulsive action of antiepileptics was not. Moreover, rimcazole (2.5 mg/kg) did not alter the total or free plasma levels of valproate or phenobarbital, so a pharmacokinetic interaction is not probable. The combined treatment of rimcazole with antiepileptic drugs, providing a 50% protection against maximal electroshock, did not affect motor performance in mice, although it resulted in significant long-term memory deficits. Our data indicate that rimcazole, in spite of lowering the seizure threshold, may enhance the protective activity of some antiepileptic drugs.
Borowicz
K K
KK
Department of Pharmacology and Toxicology, Lublin Medical University School, Poland.
Wilczyński
P M
PM
Kleinrok
Z
Z
Czuczwar
S J
SJ
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001362:Avoidance Learning / Q000187:drug effects; D002227:Carbazoles / Q000494:pharmacology*; D004056:Differential Threshold / Q000187:drug effects; D004357:Drug Synergism; D004597:Electroshock; D005260:Female; D008024:Ligands; D008568:Memory / Q000187:drug effects; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010634:Phenobarbital / Q000097:blood / Q000494:pharmacology*; D017480:Receptors, sigma / Q000378:metabolism; D014635:Valproic Acid / Q000097:blood / Q000494:pharmacology*
D000927:Anticonvulsants; D002227:Carbazoles; D008024:Ligands; D018696:Neuroprotective Agents; D017480:Receptors, sigma; D014635:Valproic Acid; C034931:rimcazole; D010634:Phenobarbital