Effect of gallamine on cholinergic receptors.

EVER SINCE the introduction of gallamine triethiodide (FlaxedilV) into clinical anaesthesia in 1948 by Huguenard and Bou6,1 there have been numerous reports of sinus tachycardia as a side effect. 2-4 Gallamine was found to have a vagolytic action localized in the heart, and for a long time it was presumed that dais was the cause of the tachycardia. 5 Recently, however, Brown and Crout ~ and Smith and Whitcher 2 have demonstrated that gallamine may cause positive inotropic and chronotropic activity in both animals and man due to the release of catecholamines from cardiac sympathetic nerves. It therefore seemed appropriate to have a closer look at the action of gallamine on the heart to see if we could demonstrate a true antiacetylcholine activity and moreover to determine if this was a competitive or non-competitive receptor interaction. As a potentiation or activation of the sympathetic nervous system would result in an antagonism similar to antimuscarinic action, it was decided to conduct these experiments in the presence of doses of propranolol hydrochloride sufficient to block cardiac sympathetic receptors. In an attempt to measure the antiacetylcholine activity of gallamine in spontaneously beating, yet sympathetically blocked hearts, in vivo preparations were chosen. To avoid the use of anaesthetics and the complications of either reflex or central actions of any of the drugs employed, pithed rats and spinally transected cats with their brains destroyed were employed.