Effect of phenytoin on cardiac slowing induced by cholinergic stimulation

Phenytoin was tested for its ability to counteract cholinergic-induced slowing in sinus rate in chloralose-anesthetized cats subjected to bilateral cervical vagotomy and spinal cord transection. The cholinergic stimuli consisted of electrical stimulation of the cervical vagus nerves and injected acetylcholine. Phenytoin administered as a continuous infusion of 0.5 and 1.0 mg/kg/min was found to significantly reduce the cardiac slowing produced by both modes of cholinergic stimulation. Blockade of the acetylcholine response suggested that the inhibitory effect of phenytoin was on the postsynaptic membrane. Measurement of serum levels of phenytoin performed in selected experiments revealed that the anticholinergic effect corresponded to plasma levels in humans exposed to therapeutic doses of this agent.