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Pharmacological reports : PR

Interactions between levetiracetam and cardiovascular drugs against electroconvulsions in mice.


PMID 25443741

Abstract

Hypertension and heart failure belong to common comorbid conditions with epilepsy so drug interactions between antiepileptics and cardiovascular drugs are possible in clinical practice. The aim of this study was to evaluate the effects of angiotensin AT1 receptor antagonists (losartan potassium and candesartan cilexetil), angiotensin-converting enzyme (ACE) inhibitors (captopril and perindopril arginine) and diuretics (hydrochlorothiazide and ethacrynic acid) on the anticonvulsant activity of levetiracetam (LEV) in mice. The protective action of LEV was examined in the maximal electroshock seizure threshold test. Drugs were administered intraperitoneally (ip). Additionally, combinations of cardiovascular drugs with LEV were tested for adverse effects in the passive avoidance task and the chimney test. Losartan potassium (50mg/kg), candesartan cilexetil (8mg/kg), captopril (50mg/kg), hydrochlorothiazide (100mg/kg) and ethacrynic acid (100mg/kg) did not affect the anticonvulsant activity of LEV. Perindopril arginine (10mg/kg) raised the convulsive threshold for LEV administered at doses of 100, 300 and 500mg/kg. This interaction could be pharmacodynamic in nature because the brain concentration of LEV remained unchanged by perindopril. The adverse effects of the combined treatment with LEV and cardiovascular drugs were not observed in the passive avoidance task or the chimney test. Although experimental data can be hardly extrapolated to clinical practice, it is suggested that perindopril arginine may positively influence the anticonvulsant action of LEV in epileptic patients. The use of losartan potassium, candesartan cilexetil, captopril, hydrochlorothiazide or ethacrynic acid in patients treated with LEV seems neutral regarding its anticonvulsant activity.