Comparison of drugs with different selectivity for central alpha 1-and alpha 2-adrenoceptors in animal models of epilepsy.
The effects of two drugs which differ in selectivity for central alpha 1- and alpha 2-adrenoceptors were compared in different animal models of epilepsy. Clonidine, a selective alpha2-adrenoceptor agonist, up to 0.5 mg/kg i.p. was inactive against electroconvulsions in mice, but decreased the threshold for electroconvulsions in rats, whereas it exerted anticonvulsant effects against seizures induced by pentylenetetrazol in mice, amygdala kindling in rats and air blast stimulation in seizure-sensitive gerbils. In gerbils, the anticonvulsant effect of clonidine was counteracted by pretreatment with the alpha2-antagonist yohimbine (2.5 mg/kg i.p.), but not by the alpha 1-selective antagonist corynanthine (10 mg/kg i.p.). St 587 [2-(2-chloro-5-trifluoromethylphenylimino)imidazolidine], a highly alpha 1-selective agonist which easily penetrates into the brain, up to 20 mg/kg i.p. exerted no effects on the thresholds for electroshock and pentylenetetrazol-induced seizures in mice and rats, but displayed significant anticonvulsant efficacy in kindled rats and epileptic gerbils. In gerbils, corynanthine but not yohimbine antagonized the anticonvulsant effect of St 587. The data indicate that, at least in certain seizure models, anticonvulsant effects can be reached via stimulation of both alpha 1- and alpha 2-adrenoceptors.
Löscher
W
W
Laboratory of Pharmacology and Toxicology, School of Veterinary Medicine, Free University of Berlin, F.R.G.
Czuczwar
S J
SJ
D000818:Animals; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004827:Epilepsy / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D005849:Gerbillinae; D007696:Kindling, Neurologic / Q000187:drug effects*; D008297:Male; D051379:Mice; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D013045:Species Specificity; D015016:Yohimbine / Q000494:pharmacology*
D011942:Receptors, Adrenergic, alpha; C030655:St 587; D015016:Yohimbine; D003000:Clonidine