A proconvulsant action of selective α2-adrenoceptor antagonists

Abstract

The effects of α 2-adrenoceptor agonists and antagonists were examined on seizure thresholds determined by intravenous infusions of convulsants in rodents. α 2-Adrenoceptor antagonists were proconvulsant; dose dependently reducing the threshold for pentylenetetrazol- or bicuculline-induced tonic seizures. Strychnine-induced tonic seizures were unaffected. The α 2-adrenoceptor agonists clonidine, BHT-933 and UK 14,304 did not modify pentylenetetazol- induced seizures at low or moderate doses but at high doses clonidine and BHT-933 were proconvulsant. The facilitatory effect of α 2-adrenoceptor antagonists on pentylenetetrazol-induced tonic seizures was blocked by clonidine or UK 14,304. The proconvulsant action of α 2-adrenoceptor antagonists was contrasted with that of ethyl-β-carboline-3-carboxylate, a benzodiazepine receptor contragonist, which markedly reduced the threshold for seizure initiation rather than the tonic seizure threshold. The selective facilitatory action of α 2-adrenoceptor blockade on tonic seizures suggests that a noradrenergic mechanism is involved in the control of seizure propagation rather than seizure initiation.