Effect of beta-adrenoceptor antagonists and some related drugs on maximal electroshock seizures in mice

(+/-) Propranolol (1-50 mg/kg), (+) propranolol (50 mg/kg) and pindolol (10-50 mg/kg) exhibited significant protective effects against MES (maximum electroshock seizures), whereas, timolol (1 mg/kg), the propranolol analog, UM-272 (1 and 10 mg/kg), and the beta-agonist, terbutaline (1 and 10 mg/kg) were ineffective. Cholinergic agents, physostigmine (0.01-1.0 mg/kg), and atropine (1 and 10 mg/kg), the serotonin antagonist, cyproheptadine (0.05 mg/kg), and the prostaglandin synthesis inhibitor, indomethacin (10 mg/kg), were also without effect on the MES extensor phase. Further, pretreatment of mice with terbutaline, atropine, cyproheptadine or indomethacin did not influence the anti-MES effect of propranolol to any significant extent. The results indicate that the observed anticonvulsant effects of beta-adrenoceptor antagonists are unrelated to noradrenergic or other central neurotransmitter systems and that a non-specific mechanism, probably a membrane stabilizing effect is involved.