Influence of 3-PPP, a sigma receptor ligand, on the anticonvulsive action of conventional antiepileptic drugs.
(+)-3-(3-Hydroxyphenyl)-N-(1-propyl)-piperidine (3-PPP; a sigma receptor ligand), administered at 30 mg kg-1, 30 min before the test, significantly decreased the electroconvulsive threshold in mice, being ineffective in lower doses. 3-PPP (20 mg kg-1) diminished the protective activity of diphenylhydantoin, phenobarbital and valproate, but not that of carbamazepine against maximal electroshock. The effect of 3-PPP upon the electroconvulsive threshold and the 3-PPP-induced inhibition of the protective action of antiepileptics was reversed by haloperidol (0.5 mg kg-1). Moreover, 3-PPP did not alter the total and free plasma levels of antiepileptic drugs, so a pharmacokinetic interaction is not probable. The combined treatment of 3-PPP with antiepileptic drugs, providing a 50% protection against maximal electroshock, did not affect motor performance in mice, although resulted in significant long-term memory deficits. Our data indicate that sigma receptor-mediated events may play some role in seizure processes in the central nervous system and can modulate the protective activity of some conventional antiepileptic drugs.
Borowicz
K K
KK
Department of Pharmacology and Toxicology, Lublin Medical University School, Poland.
Kleinrok
Z
Z
Czuczwar
S J
SJ
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001362:Avoidance Learning / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000494:pharmacology; D005260:Female; D006146:Guanidines / Q000494:pharmacology; D051379:Mice; D010634:Phenobarbital / Q000097:blood; D010880:Piperidines / Q000494:pharmacology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D017480:Receptors, sigma / Q000187:drug effects / Q000502:physiology*; D014635:Valproic Acid / Q000097:blood
D000927:Anticonvulsants; D006146:Guanidines; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; D017480:Receptors, sigma; D014635:Valproic Acid; D016291:Dizocilpine Maleate; C026539:preclamol; C050232:1,3-ditolylguanidine; D010634:Phenobarbital