A proconvulsant action of selective alpha 2-adrenoceptor antagonists.

The effects of alpha 2-adrenoceptor agonists and antagonists were examined on seizure thresholds determined by intravenous infusions of convulsants in rodents. alpha 2-Adrenoceptor antagonists were proconvulsant; dose dependently reducing the threshold for pentylenetetrazol- or bicuculline-induced tonic seizures. Strychnine-induced tonic seizures were unaffected. The alpha 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 alpha 2-adrenoceptor antagonists on pentylenetetrazol-induced tonic seizures was blocked by clonidine or UK 14,304. The proconvulsant action of alpha 2-adrenoceptor antagonists was contrasted with that of ethyl-beta-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 alpha 2-adrenoceptor blockade on tonic seizures suggests that a noradrenergic mechanism is involved in the control of seizure propagation rather than seizure initiation.