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.
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.
Isobolographic Analysis Laboratory, Institute of Agricultural Medicine, Lublin, Poland.
Marta
M
Andres-Mach
Agnieszka
A
Haratym-Maj
Mirosław
M
Zagaja
Jarogniew J
JJ
Luszczki
D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000494:pharmacology*; D001569:Benzodiazepines / Q000008:administration & dosage / Q000494:pharmacology*; D000078306:Clobazam; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004597:Electroshock; D008297:Male; D051379:Mice; D012640:Seizures / Q000188:drug therapy* / Q000503:physiopathology; D044005:Tetrahydroisoquinolines / Q000008:administration & dosage / Q000494:pharmacology*
D000927:Anticonvulsants; D044005:Tetrahydroisoquinolines; D001569:Benzodiazepines; D000078306:Clobazam; C050386:1-methyl-1,2,3,4-tetrahydroisoquinoline