Drug-induced depression of gamma efferent activity—III. Viscero-somatic reflex action of phenyldiguanide, veratridine and 5-hydroxytryptamine

Phenyldiguanide and veratridine given i.v. in doses of 25–60 and 12–30 μg/kg, respectively, were found to produce depression preceded by brief acceleration of spontaneous γ efferent and attendant spindle afferent discharge in cats under chloralose-urethane anesthesia. This effect resembles that described earlier for nicotine. The depressant action of phenyldiguanide and veratridine, which occurred in both extensor and flexor γ fibers, was abolished by bilateral cervical vagotomy or spinal transection, suggesting that it was caused by a reflex action arising from sensory receptors in the cardiopulmonary region. The γ acceleratory effect, on the other hand, which was not entirely prevented by vagotomy, is likely to originate from more widely distributed sensory receptors including cutaneous endings. Excitation of cardiopulmonary receptors causes the autonomic effects of phenyldiguanide and veratridine (bradycardia, hypotension and apnea). The simultaneous onset of hypotension and γ depression, as well as other observations, indicate that the γ depression cannot be due to the fall in blood pressure and that, for a given drug, both effects may be due to excitation of the same sensory ending. Since receptors in different portions of the cardiopulmonary region have been implicated in the autonomic reflex effects of phenyldiguanide, veratridine and nicotine, the same would then hold true for the γ depressant action of these drugs. The γ depression elicited by phenyldiguanide was abolished by naphthylguanidine, sparing the effects of veratridine and nicotine; the γ depression elicited by nicotine was blocked by hexamethonium, sparing the effects of phenyldiguanide and veratridine. This selective antagonism suggests the existence of distinct pharmacological receptor sites situated on the sensory endings excited by the drugs, γ Acceleration, rather than depression, was the predominant effect of i.v. injection of 5-hydroxytryptamine. This effect also was probably due to stimulation of sensory endings, since it was abolished by blockade of the neuronal M receptors with morphine.