The influence of certain ganglionic blocking agents on neuromuscular transmission.

GANGLIONIC blockade was first used to produce controlled hypotension during surgery by Scurr (1951). This technique has since become generally accepted in anaesthetic practice. Ganglion blocking drugs now available include the methonium compounds and the short acting agents trimetaphan and homatropinium (Trophenium). There is no doubt that these drugs act selectively on the sympathetic ganglia, which is, perhaps, surprising in view of the similar humoral transmission mechanism thought to operate at other synapses and also at the motor endplates. Biilbring and Depierre (1949) suggested that the differences in the physiological mechanisms at sympathetic ganglia and the neuromuscular junction are quantitative rather than qualitative, and Paton (1954) considers the anatomical differences enough to account for dissimilarities in the actions of drugs at the two sites. It seems likely that a drug which is active at sympathetic ganglia would, in sufficient concentration, be effective at the motor endplate (and vice versa). The methonium compounds have been shown to have a neuromuscular blocking action in very large doses by Barlow and Ing (1948) and by Paton and Zaimis (1948). These workers showed that as the length of the chain between the quaternary nitrogen atoms decreases, so does the neuromuscular blocking effect diminish, being at its least in the hexane and pentane derivatives. However, large doses of hexamethonium will produce "head-drop" in the rabbit, and this effect is potentiated by curare. With regard to trimetaphan, Acheson and Pereira (1946) stated that this drug had no curarelike effect. Randall et al. (1949) agreed with this observation and considered a slight muscular 217 weakness noted in dogs to be due to the deficient blood supply caused by the hypotension. It is interesting to note that nearly all the animals which received a lethal dose of trimetaphan died of respiratory failure. Tewfik (1957), noting a prolongation of suxamethonium apnoea in patients also receiving trimetaphan, suggested that trimetaphan has some slight muscle-paralyzing effect and may be destroyed by pseudocholinesterase. Payne (1957) has recently shown that trimetaphan has a weak neuromuscular blocking effect in cats previously given mecamylamine. In the case of homatropinium, large doses are reported by Robertson et al. (1957) to produce respiratory paralysis in mice, rats, rabbits and cats. This may indicate the possibility of neuromuscular block occurring with this drug also. Recent clinical experience has led us to believe that the effect of ganglion blocking drugs on neuromuscular transmission may be of practical importance. Accordingly, we decided to investigate and compare this effect in the case of hexamethonium, trimetaphan and homatropinium.