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• W1979666564 abstract "It was previously documented that calcium (Ca2+) channel inhibitors intensified the protective effects of conventional antiepileptics against electroconvulsions in mice. The aim of this study was to evaluate the effects of Ca2+ channel inhibitors (nifedipine, nicardipine and flunarizine) on the anticonvulsant action of the new AMPA/kainate receptor antagonist, 7-acetyl-3-(4-aminophenyl)-8,9-dihydro-8-methyl-7H-1,3-dioxazolo[4,5-h][2,3]-benzodiazepine (LY 300164), against maximal electroshock (MES)-induced seizures in mice. Dantrolene (an inhibitor of Ca2+release from intracellular stores) was also included. Nifedipine (30 mg/kg) and flunarizine (15 mg/kg) raised the threshold for electroconvulsions, being ineffective at lower doses. Nicardipine (up to 30 mg/kg) and dantrolene (up to 20 mg/kg) did not affect this parameter. Flunarizine (10 mg/kg), nicardipine (20 mg/kg) and dantrolene (20 mg/kg) potentiated the efficacy of LY 300164 against MES. However, nicardipine (at 20 mg/kg) raised the free plasma concentration of LY 300164. Nifedipine (30 mg/kg), given even in a dose raising the electroconvulsive threshold, did not significantly alter the protective effect of LY 300164 against MES. Furthermore, the Ca2+ channel agonist—BAY k-8644 (at 5 mg/kg) did not influence the protection offered by LY 300164 against MES. Finally, this Ca2+ channel activator did not affect the enhanced efficacy of LY 300164 by Ca2+ channel modulators. The only exception was the combination of LY 300164 with flunarizine. Combined treatment with LY 300164 and dantrolene (20 mg/kg), compared to LY 300164 alone, resulted in an impairment of motor performance in mice. Ca2+ channel inhibitors were without effect upon this parameter evaluated in the chimney test. As shown in the passive avoidance task, LY 300164 alone (at its ED50) or combined with agents affecting neuronal Ca2+ concentration did not disturb long-term memory. The present results suggest that agents preventing influx of Ca2+ ions into neurons may enhance the protective action of LY 300164." @default.
• W1979666564 created "2016-06-24" @default.
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• W1979666564 date "2002-08-01" @default.
• W1979666564 modified "2023-10-02" @default.
• W1979666564 title "Influence of agents affecting voltage-dependent calcium channels and dantrolene on the anticonvulsant action of the AMPA/kainate receptor antagonist LY 300164 in mice" @default.
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• W1979666564 doi "https://doi.org/10.1016/s0924-977x(02)00045-7" @default.
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