beta-adrenoceptor blockade enhances the anticonvulsant effect of glutamatereceptor antagonists against maximal electroshock

In this study, we evaluated whether beta -adrenoceptor antagonists may modi fy the protective efficacy of dizocilpine (MK-801), a NMDA receptor antagon ist, and 1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepin e (GYKI 52466), a non-NMDA (AMPA/kainate) receptor antagonist, against maxi mal electroshock-induced seizures in mice. Propranolol, acebutolol, metopro lol and atenolol were used in doses that did not alter the electroconvulsiv e threshold. Propranolol potentiated the anticonvulsant activity of MK-801 and GYKI 52466, significantly lowering their ED50 values from 0.38 and 15.0 to 0.15 (P < 0.001) and 8.4 mg/kg (P < 0.001), respectively. Similarly, me toprolol lowered the ED50 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 ED50 value from 15.0 to 12.2 mg/kg (P < 0.05), but not that of MK-801. Atenolol, not penetrating the blood-brain b arrier, did not affect the anticonvulsive efficacy of MK-801 and GYKI 52466 . In conclusion, beta -adrenoceptor antagonists may act synergistically wit h excitatory amino acid receptor antagonists to inhibit generalised tonic-c lonic seizures. (C) 2001 Elsevier Science B.V. All rights reserved.