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.
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001640:Bicuculline; D002243:Carbolines / Q000494:pharmacology; D003292:Convulsants; D008297:Male; D051379:Mice; D010433:Pentylenetetrazole; D051381:Rats; D011919:Rats, Inbred Strains; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology; D013331:Strychnine
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D002243:Carbolines; D003292:Convulsants; C024915:beta-carboline-3-carboxylic acid ethyl ester; D013331:Strychnine; D010433:Pentylenetetrazole; D001640:Bicuculline