||Examination of the Anticonvulsant Properties of Voltage-Sensitive Calcium Channel Inhibitors in Amygdala Kindled Seizures.
Mack, C. M. ;
Bilbert., M. E. ;
||ManTech Environmental Technology, Inc., Research Triangle Park, NC.;Health Effects Research Lab., Research Triangle Park, NC.
Calcium channel blockers ;
Dose-response relationships ;
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||Representatives from three different classes of voltage-sensitive calcium (VSC) channel inhibitors were assessed for their protection against amygdala kindled seizures. Adult male Long Evans rats (n=12) were implanted with electrodes in the amygdala and were stimulated once daily until generalized stage 5 seizures (GS) were observed. Subsequently a minimum stimulus intensity required to evoke a GS was determined. The Ca(sup 2+)-channel antagonists (nimodipine 0,5,25,50 mg/kg; nitrendipine 0,25,50,100 mg/kg; verapamil 0,10,20,40 mg/kg and flunarizine 0,20,40,80 mg/kg) were administered po 60-90 mins prior to amygdala stimulation at the established threshold. None of the drugs altered threshold for inducing a seizure. The phenylalkylamine, verapamil, and the dihydropyridines nimodipine and nitrendipine, were without effect on amygdala kindled seizures. The diphenylalkylamine flunarizine (80 mg/kg) produced a significant reduction in seizure severity (25%), AD duration (63%), and duration of clonic seizure activity (69%). It was concluded that non-NMDA Ca(sup 2+)-channel antagonists do possess anticonvulsant properties and do so in the absence of any overt signs of toxicity. The diphenylalkylamine flunarizine is the most efficacious. Thus voltage sensitive Ca(sup 2+)-channels, distinct from the NMDA mediated channel, may contribute to epileptiform activity induced by kindling. (Copyright (c) Springer-Verlag 1992.)
||Pub. in Psychopharmacology, v106 n3 p365-369 Mar 92. Sponsored by Health Effects Research Lab., Research Triangle Park, NC.
|NTIS Title Notes
||Reprint: Examination of the Anticonvulsant Properties of Voltage-Sensitive Calcium Channel Inhibitors in Amygdala Kindled Seizures.
||PC A02/MF A01