Muscle relaxation by drugs which stimulate sensory nerve endings—II. The effect of nicotinic agents

Abstract

Nicotine, given by i.v. or right intra-atrial injection in doses of 10–40 μg/kg, depressed the “spontaneous” electrical activity and tone in both extensor and flexor muscles of cats rendered rigid by intercollicular decerebration and in intact preparations under light chloraloseurethane anaesthesia. The latent periods of this action following intra-atrial injection varied from 1 to 2 sec, indicating that it must have originated from receptors located between the right atrium and the pulmonary capillary bed. The onset of the reflex motor depression frequently coincided with the onset of the vagovagal cardiodecelerator-hypotensive response, suggesting that both effects arose from the same type of receptor. These brief latency effects were dependent on vagal afferents. After vagotomy a motor depressant effect with delayed onset was seen. Instances of differential abolition, or absence, of the effect of nicotine and phenyldiguanide under varying conditions of decerebration and anesthesia suggest that the motor depressant effect of nicotine does not arise from the pulmonary deflation receptors, responsible for the effect of phenyldiguanide, but is initiated at the pulmonary arterial baroreceptors which have earlier been implicated in the hypotensive reflex response to nicotine. The motor depressant effect of nicotine was duplicated by the quaternary nicotinic agent sebacylcholine and also by acetylcholine, and was blocked by hexamethonium, confirming the peripheral reflex nature of the effect. Neuromuscular transmission was not impaired in the doses used. Dihydro-β-erythroidine, blocking the nicotinic synapse at the Renshaw interneuron, reduced or abolished the inhibition by nicotine of the knee jerk but had little influence on the reflex motor depression, while hexamethonium had the reverse effect. Thus, Renshaw inhibition was responsible for much of the depressant action of nicotine on the knee jerk but played only a minor part in the reflex motor depression. In several experiments hexamethonium itself depressed motor activity by an as yet unexplained mechanism.