ROLE OF CENTRAL β‐ADRENOCEPTORS IN THE CONTROL OF PENTYLENETETRAZOL‐INDUCED CONVULSIONS IN RATS

Abstract

The role of central β‐adrenoceptors in the anticonvulsant effect of β‐adrenoceptor antagonists has been examined. 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. At the EC5+ level, (−)‐propranolol is seven times more effective than the (+)‐isomer. Oral administration of (−)‐, (+)‐or (±)‐practolol (1–10 mg/kg) or (−)‐or (+)‐timolol (1–10 mg/kg), two β‐adrenoceptor antagonists that do not penetrate the blood brain barrier, had no significant effect on the duration of PTZ‐induced convulsions. Intracerebroventricular administration of (−)‐propranolol (0.5 μg/kg) or (−)‐timolol (0.25 μg/kg) produced highly significant anticonvulsant effects whereas the (+)‐isomers at the same dose level were ineffective. (±)‐Pindolol (0.25 μg/kg) was also much more effective given by this route than when given orally. The (+)‐and (−)‐isomers of the β1‐adrenoceptor selective antagonist practolol (10 μg/kg) exerted only weak anticonvulsant effects. This study provides evidence that β‐adrenoceptor antagonists exert an anticonvulsant effect through central β2‐adrenoceptors. At high dose levels, additional anticonvulsant activity is associated with membrane stabilization in those antagonists which possess this property. 1982 British Pharmacological Society