EFFECTS OF DILTIAZEM IN CONVULSIVE STATES DIFFER FROM THOSE PREVIOUSLY REPORTED FOR DIHYDROPYRIDINE CALCIUM-CHANNEL ANTAGONISTS

Unlike the dihydropyridine calcium channel antagonists studied previou sly, the benzothiazepine calcium channel antagonist, diltiazem, increa sed the incidence of convulsions caused by bicuculline, N-methyl-DL-as partate or 4-aminopyridine. However, the latencies to convulsions were also increased. Diltiazem increased the ratings of convulsive behavio ur on handling after intraperitoneal administration of bicuculline, or pentylenetetrazol and after the calcium channel;activator, Bay K 8644 , administered ICV. When the binding of the dihydropyridine, [H-3]-nit rendipine in the CNS was measured in vivo, this was increased by dilti azem. This compound therefore showed a different pattern of interactio n with convulsant drugs then that previously demonstrated for other ca lcium channel antagonists, appearing to possess both pro- and anticonv ulsant actions, and a different pattern of interaction with the dihydr opyridine receptor complex.