β-Adrenoceptor blockade enhances the anticonvulsant effect of glutamate receptor antagonists against maximal electroshock

Abstract

In this study, we evaluated whether β-adrenoceptor antagonists may modify the protective efficacy of dizocilpine (MK-801), a NMDA receptor antagonist, and 1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine (GYKI 52466), a non-NMDA (AMPA/kainate) receptor antagonist, against maximal electroshock-induced seizures in mice. Propranolol, acebutolol, metoprolol and atenolol were used in doses that did not alter the electroconvulsive threshold. Propranolol potentiated the anticonvulsant activity of MK-801 and GYKI 52466, significantly lowering their ED 50 values from 0.38 and 15.0 to 0.15 ( P<0.001) and 8.4 mg/kg ( P<0.001), respectively. Similarly, metoprolol lowered the ED 50 of MK-801 and GYKI 52466 from 0.38 and 15.0 to 0.17 ( P<0.05) and 11.2 mg/kg ( P<0.05). Acebutolol enhanced the protective action of GYKI 52466, lowering its ED 50 value from 15.0 to 12.2 mg/kg ( P<0.05), but not that of MK-801. Atenolol, not penetrating the blood–brain barrier, did not affect the anticonvulsive efficacy of MK-801 and GYKI 52466. In conclusion, β-adrenoceptor antagonists may act synergistically with excitatory amino acid receptor antagonists to inhibit generalised tonic-clonic seizures.