RESUMO
There is evidence that some calcium (Ca(2+)) channel inhibitors enhance the protective activity of antiepileptic drugs. Since clinical trials have not provided consistent data on this issue, the objective of this study was to evaluate the interaction of a dihydropyridine, niguldipine, with conventional antiepileptics in amygdala-kindled rats. Niguldipine (at 7.5 but not at 5 mg/kg) displayed a significant anticonvulsant effect, as regards seizure and afterdischarge durations in amygdala-kindled convulsions in rats, a model of complex partial seizures. No protective effect was observed when niguldipine (5 mg/kg) was combined with antiepileptics at subeffective doses, i.e. valproate (75 mg/kg), diphenylhydantoin (40 mg/kg), or clonazepam (0.003 mg/kg). Unexpectedly, the combined treatment of niguldipine (5 mg/kg) with carbamazepine (20 mg/kg) or phenobarbital (20 mg/kg) resulted in a proconvulsive action. BAY k-8644 (an L-type Ca(2+) channel activator) did not modify the protective activity of niguldipine (7.5 mg/kg) or the opposite action of this dihydropyridine (5 mg/kg) in combinations with carbamazepine or phenobarbital. A pharmacokinetic interaction is not probable since niguldipine did not affect the free plasma levels of the antiepileptics. These data indicate that the opposite actions of niguldipine alone or combined with carbamazepine (or phenobarbital) were not associated with Ca(2+) channel blockade. The present results may argue against the use of niguldipine as an adjuvant antiepileptic or for cardiovascular reasons in patients with complex partial seizures.
Assuntos
Tonsila do Cerebelo/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/farmacologia , Carbamazepina/antagonistas & inibidores , Di-Hidropiridinas/farmacologia , Excitação Neurológica/efeitos dos fármacos , Fenobarbital/antagonistas & inibidores , Convulsões/tratamento farmacológico , Éster Metílico do Ácido 3-Piridinacarboxílico, 1,4-Di-Hidro-2,6-Dimetil-5-Nitro-4-(2-(Trifluormetil)fenil)/administração & dosagem , Éster Metílico do Ácido 3-Piridinacarboxílico, 1,4-Di-Hidro-2,6-Dimetil-5-Nitro-4-(2-(Trifluormetil)fenil)/farmacologia , Tonsila do Cerebelo/fisiologia , Animais , Anticonvulsivantes/antagonistas & inibidores , Anticonvulsivantes/sangue , Anticonvulsivantes/farmacologia , Anticonvulsivantes/uso terapêutico , Agonistas dos Canais de Cálcio/administração & dosagem , Agonistas dos Canais de Cálcio/farmacologia , Carbamazepina/sangue , Carbamazepina/farmacologia , Carbamazepina/uso terapêutico , Combinação de Medicamentos , Injeções Intraperitoneais , Excitação Neurológica/fisiologia , Masculino , Fenobarbital/sangue , Fenobarbital/farmacologia , Fenobarbital/uso terapêutico , Ratos , Ratos WistarRESUMO
The anti-diuretic action of carbamazepine, before and after concurrent treatment with demeclocycline, has been studied in a single epileptic subject, in whom two episodes of status epilepticus had been associated with excessive fluid intake and hyponatraemia. After addition of demeclocyline, free water clearance, plasma arginine vasopressin concentration and serum osmolality (all appreciably reduced after carbamazepine alone) increased but did not revert to normal. The findings are consistent with direct antagonism by demeclocycline of the enhancing effect of carbamazepine on endogenous ADH activity.