Some studies suggest a higher risk of
hypertension in people with
epilepsy.
Captopril, a potent and selective
angiotensin-converting enzyme (
ACE) inhibitor, is a well known
antihypertensive drug. Besides the peripheral renin-angiotensin system (RAS),
ACE inhibitors are also suggested to affect the brain RAS which might participate in the regulation of seizure susceptibility. The purpose of the current study was to evaluate the effect of
captopril on the protective action of numerous
antiepileptic drugs (
carbamazepine [CBZ],
phenytoin [PHT],
valproate [VPA],
phenobarbital [PB],
oxcarbazepine [OXC],
lamotrigine [LTG] and
topiramate [TPM]) against maximal electroshock-induced
seizures in mice. This study was accompanied by an evaluation of adverse effects of combined treatment with
captopril and
antiepileptic drugs in the passive avoidance task and chimney test.
Captopril (25 and 50 mg/kg i.p.) did not influence the threshold for electroconvulsions. Among the tested
antiepileptics,
captopril (25 and 50 mg/kg i.p.) potentiated the antiseizure action of CBZ, decreasing its ED(50) value from 12.1 to 8.9 and 8.7 mg/kg, respectively. Moreover,
captopril (50 mg/kg i.p.) enhanced the
anticonvulsant activity of LTG. ED(50) value for LTG was lowered from 5.1 to 3.5 mg/kg. The observed interactions between
captopril and CBZ or LTG were pharmacodynamic in nature as
captopril did not alter plasma and total brain concentrations of these
antiepileptics. The combinations of
captopril with
antiepileptic drugs did not lead to retention deficits in the passive avoidance task or motor impairment in the chimney test. Based on the current preclinical data, it is suggested that
captopril may positively interact with CBZ and LTG in epileptic patients. The combinations of
captopril with the remaining
antiepileptics (PHT, VPA, PB, OXC and TPM) seem neutral.