Evaluation of the combined treatment with pregabalin and inhibitors of the renin-angiotensin system against maximal electroshock in mice

Abstract

Łukawski K, Raszewski G, Czuczwar S. J. Evaluation of the combined treatment with pregabalin and inhibitors of the renin-angiotensin system against maximal electroshock in mice. J Pre-Clin Clin Res. 2018; 12(2): 63-66. doi: 10.26444/jpccr/91611 Abstract Introduction and objective. Hypertension is a common comorbid condition in patients with epilepsy. Combined treatment with antiepileptic drugs (AEDs) and antihypertensives may lead to pharmacokinetic and/or pharmacodynamic interactions. The purpose of the current study was to examine the effects of angiotensin-converting enzyme (ACE) inhibitors (captopril and perindopril) and angiotensin AT 1 receptor antagonists (losartan and candesartan) on the anticonvulsant activity of pregabalin in the maximal electroshock seizure (MES) test in mice. Materials and method. The study was conducted on adult Swiss mice. Drugs were administered intraperitoneally. Electroconvulsions (50 Hz, 500 V, current intensity 25 mA) were produced by a Hugo Sachs generator. Additionally, adverse effects of the combined treatment were assessed in the step-through passive avoidance task and the chimney test. Results. Captopril (50 mg/kg), perindopril (10 mg/kg), losartan (50 mg/kg) and candesartan (8 mg/kg) did not affect the anticonvulsant action of pregabalin in the MES test. In the chimney test, the combinations of pregabalin (315.7 mg/kg) with losartan (50 and 25 mg/kg) significantly impaired motor coordination in mice, P<0.001 and P<0.05, respectively. Combinations of pregabalin with other antihypertensives were ineffective in this test. In the passive avoidance task, co-administration of pregabalin with antihypertensives showed a strong tendency towards impaired retention. Conclusions. It is suggested that the use of pregabalin with the examined antihypertensive drugs in patients with epilepsy is presumed neutral regarding anticonvulsant action of pregabalin. However, caution is advised during co-administration of pregabalin with losartan at high doses due to neurotoxicity in mice.