Canadian Journal of Anesthesia, Vol 8, 335-346, Copyright © 1961 by Canadian Anesthesiologists' Society

Central Effects of Five Muscle Relaxants

¹ Departments of Pharmacology and Anaesthesia, Faculty of Medicine, University of Western Ontario, London, Canada

Fifteen experiments utilizing cross-circulated healthy dogs were performed to investigate the purely central action of succinylcholine chloride, decamethonium, d-tubocurarine chloride, gallamine tri-ethiodide, and 1,6-hexamethylene-biscarbaminoylcholine bromide.

The experiments were conducted under conditions of normothermia and controlled oxygenation and perfusion pressure to reduce the variables influencing the central nervous system.

All the relaxant drugs used were considered to, exhibit central activity, apart from their well-known activity at the myonerual junction. Hexamethylenecarbaminoylcholine, in particular, appeared to exert a marked central action because of it's ability to permeate the blood-brain barrier with relative ease.

By far the most significant central effect was on the respiratory centre,causing depression and apnoea in the isolated receipient body. The dosage required to produce a peripheral myoneural block in the donor body.

Significant tachyphylaxis was observed only with decamethonium, where it was difficult to effect myoneural block and long-lasting central respiratory depression.

Vasomotor effects were not noted except with d-tubocurare: increasing doses resulted in increasing hypotension.

Cerebral stimulation was elicited in two of the three decamethonium experiments, one of three curare experiments, and one of four hexamethylene carbaminoylcholine experiments.

No cardiac effects attributable to these Agents were noted. A hypothesis for the possible action of hexamethylene carbaminoylcholine is suggested inthe light of the results obtained in these experiments and from other published clinical reports. Further work in this field is indicated.

The increasing significance of altered body economy and the increased scope and extent of surgery in the presence of such conditions suggest to us that the side-effects of muscle relaxants may come to assume a more significant role than previously.

Species variation in the effects of myoneural blocking agents undoubtedly occurs, but it is felt that the present study, combined with the clinical appraisals, leads to the belief that central activity can indeed be significant in certain cases.

The nebulous blood-brain barrier offers a wide field for further investigation.

Note:

A preliminary report of this work was presented at the 1960 Fall Meeting of the American Society for Pharmacology and Experimental Therapeutics (Hersey, L. W., The Pharmacologist 2: 86 [1960]).