Additive Interactions between 1-Methyl-1,2,3,4-Tetrahydroisoquinoline and Clobazam in the Mouse Maximal Electroshock-Induced Tonic Seizure Model - An Isobolographic Analysis for Parallel Dose-Response Relationship Curves

作者：Andres Mach Marta^*; Haratym Maj Agnieszka; Zagaja Miroslaw; Luszczki Jarogniew J

来源：Pharmacology, 2014, 93(3-4): 172-177.

DOI：10.1159/000360640

• Clobazam
• Maximal electroshockinduced seizures
• 1Methyl1,2,3,4tetrahydroisoquinoline
• Pharmacokinetic/pharmacodynamic interactions

Background: The aim of this study was to characterize the anticonvulsant effect of 1-methyl-1,2,3,4-tetrahydroisoquinoline (1-MeTHIQ) in combination with clobazam (CLB) in the mouse maximal electroshock-induced seizure (MES) model. Methods: The anticonvulsant interaction profile between 1-MeTHIQ and CLB in the mouse MES model was determined using an isobolographic analysis for parallel dose-response relationship curves. Results: Electroconvulsions were produced in albino Swiss mice by a current (sine wave, 25 mA, 500 V, 50 Hz, 0.2-second stimulus duration) delivered via auricular electrodes by a Hugo Sachs generator. There was an additive effect of the combination of 1-MeTHIQ with CLB (at the fixed ratios of 1: 3, 1: 1 and 3: 1) in the mouse MES-induced tonic seizure model. Conclusions: The additive interaction of the combination of 1-MeTHIQ with CLB (at fixed-ratios of 1: 3, 1: 1 and 3: 1) in the mouse MES model seems to be pharmacodynamic in nature and worth of considering in further clinical practice.

• 出版日期2014