期刊
EUROPEAN JOURNAL OF PHARMACOLOGY
卷 602, 期 2-3, 页码 298-305出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejphar.2008.11.049
关键词
1-Methyl-1,2,3,4-tetrahydroisoquinoline; Antiepileptic drugs; Isobolographic analysis; Maximal electroshock; Pharmacodynamic/pharmacokinetic interaction
资金
- Institute of Agricultural Medicine and Medical University of Lublin
The anticonvulsant activity of 1-methyl-1,2,3,4-tetrahydroisoquinoline (MeTHIQ - an endogenous parkinsonism-preventing substance) administered alone and in combination with four conventional antiepileptic drugs (carbamazepine, phenytoin, phenobarbital and valproate) was determined in the mouse maximal electroshock-induced seizure model. The types of interactions of MeTHIQ with the antiepileptic drugs were characterized using isobolographic analysis. The isobolographic analysis revealed that the combination of MeTHIQ with phenobarbital at the fixed-ratios of 1:3, 1:1 and 3:1 exerted supra-additive (synergistic) interaction in the maximal electroshock-induced seizure test. In contrast, the combinations of MeTHIQ with carbamazepine, phenytoin and valproate exerted additive interaction for all three fixed-ratios (1:3, 1:1 and 3:1) tested in the maximal electroshock-induced seizure test. In conclusion, MeTHIQ produces a clear-cut anticonvulsant effect in the maximal electroshock-induced seizure test in mice. The supra-additive interaction of MeTHIQ with phenobarbital against maximal electroshock-induced seizures makes their combination of pivotal importance from a clinical viewpoint. (C) 2008 Elsevier B.V. All rights reserved.
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