Role of voltage dependent calcium channels and cholinergic receptors in the convulsant action of BAY k-8644.

The study was designed to investigate the effects of administration of cholinomimetic agents and nifedipine on seizures induced by BAY k-8644 in rats. Injection of pilocarpine (3 mg/kg) increased seizures induced by BAY k-8644 (2 mg/kg). Administration of nifedipine (10 mg/kg) did not affect the convulsions and mortality elicited by coadministration of BAY k-8644 and pilocarpine. However, the facilitating effect of pilocarpine on BAY k-8644-induced seizures was fully prevented by pretreatment of rats with a cholinergic antagonist atropine (5 mg/kg). No similar effects were observed after injection of another cholinomimetic agent physostigmine (0.3 mg/kg). This finding implies, that facilitation of convulsant action of BAY k-8644 by pilocarpine may be related to activity of cholinergic system, but not strictly to activity of voltage dependent calcium channels.