Assessment of combined treatment with vigabatrin and antihypertensive drugs against electroconvulsions in mice
Journal Title: Journal of Pre-Clinical and Clinical Research - Year 2015, Vol 9, Issue 1
Abstract
[b]Introduction and objective[/b]. It is likely that cardiovascular drugs will be used in epileptic patients because heart failure and hypertension are common comorbid conditions with epilepsy. Experimental studies show that some cardiovascular drugs can affect the protective activity of antiepileptics. [b]Objective[/b]. The aim of this study was to examine the effects in mice of angiotensin-converting enzyme (ACE) inhibitors (captopril and perindopril), angiotensin AT1 receptor antagonists (losartan and candesartan) and diuretics (hydrochlorothiazide and ethacrynic acid) on the anticonvulsant activity of vigabatrin (VGB), a second generation antiepileptic drug. [b]Materials and methods[/b]. Adult Swiss mice were used in the study. The anticonvulsant action of VGB was assessed in the maximal electroshock seizure threshold test. Combined treatment with VGB and antihypertensive drugs was also tested for adverse effects in the passive avoidance task and chimney test. All drugs were administered intraperitoneally. [b]Results.[/b] Captopril (50 mg/kg), perindopril (10 mg/kg), losartan (50 mg/kg), candesartan (8 mg/kg), hydrochlorothiazide (100 mg/kg) and ethacrynic acid (100 mg/kg) did not influence the protective action of VGB. The combined treatment with VGB (700 mg/kg) and antihypertensive drugs showed a strong tendency towards impaired retention in the passive avoidance task, and in the case of the combination of VGB with ethacrynic acid it reached statistical significance (P < 0.05). Mice were not disturbed in the chimney test following applied treatment. [b]Conclusions[/b]. From the preclinical point of view, the use of the tested antihypertensive drugs in patients treated with VGB seems neutral regarding its anticonvulsant activity.
Authors and Affiliations
Krzysztof Łukawski, Grzegorz Raszewski, Stanislaw Czuczwar
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