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 diphenyl...

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Bibliographic Details
Published inPharmacological research Vol. 40; no. 6; pp. 509 - 516
Main Authors BOROWICZ, K.K., KLEINROK, Z., CZUCZWAR, S.J.
Format Journal Article
LanguageEnglish
Published Netherlands Elsevier Ltd 01.12.1999
Subjects
3-PPP, sigma ligand, sigma receptor, antiepileptic drugs, electroshock maximal, seizures
Animals
Anticonvulsants - pharmacology
Avoidance Learning - drug effects
Dizocilpine Maleate - pharmacology
Female
Guanidines - pharmacology
Mice
Phenobarbital - blood
Piperidines - pharmacology
Receptors, N-Methyl-D-Aspartate - physiology
Receptors, sigma - drug effects
Receptors, sigma - physiology
Valproic Acid - blood
3-PPP, sigma ligand, sigma receptor, antiepileptic drugs, electroshock maximal, seizures
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Summary:(+)-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.pc 1999 Academic Press@p$hr
ISSN:1043-6618
1096-1186
DOI:10.1006/phrs.1999.0548