Role of central beta-adrenoceptors in the control of pentylenetetrazol-induced convulsions in rats.
1 The role of central beta-adrenoceptors in the anticonvulsant effect of beta-adrenoceptor antagonists has been examined. 2 Oral administration of (-)- and (+)-propranolol (0.05-1 mg/kg) and (+/-)-pindolol (0.025-0.5 mg/kg) produced a dose-dependent decrease in duration of convulsions produced by pentylenetetrazol (PTZ 50 mg/kg, i.p.) in rats. 3 At the EC50 level, (-)-propranolol is seven times more effective than the (+)-isomer. 4 Oral administration of (-)-, (+)- or (+/-)-practolol (1-10 mg/kg) or (-)- or (+)-timolol (1-10 mg/kg), two beta-adrenoceptor antagonists that do not penetrate the blood brain barrier, had no significant effect on the duration of PTZ-induced convulsions. 5 Intracerebroventricular administration of (-)-propranolol (0.5 microgram/kg) or (-)-timolol (0.25 microgram/kg) produced highly significant anticonvulsant effects whereas the (+)-isomers at the same dose level were ineffective. (+/-)-Pindolol (0.25 microgram/kg) was also much more effective given by this route than when given orally. The (+)- and (-)-isomers of the beta 1-adrenoceptor selective antagonist practolol (10 microgram/kg) exerted only weak anticonvulsant effects. 6 This study provides evidence that beta-adrenoceptor antagonists exert an anticonvulsant effect through central beta 2-adrenoceptors. At high dose levels, additional anticonvulsant activity is associated with membrane stabilization in those antagonists which possess this property.
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants; D005260:Female; D007276:Injections, Intraventricular; D008297:Male; D010433:Pentylenetetrazole / Q000494:pharmacology*; D010869:Pindolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology*
D000319:Adrenergic beta-Antagonists; D000927:Anticonvulsants; D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; D010869:Pindolol; D010433:Pentylenetetrazole