Summary
Gallamine triethiodide causes tachycardia thought to be due to a specific vagolytic action. Recently, Brown and Crout have shown that gallamine may cause increased inotropic and chronotropic activity due to the release of catecholamines from cardiac sympathetic nerves. As a further analysis of the mechanisms, experiments were performed on pithed rats and spinally transected, braindestroyed catsin vivo pretreated with hexamethonium and/or propranolol to determine the nature of the antiacetylcholine action of gallamine on the heart.
A significant antagonism by gallamine of the negative chronotropic action of acetylcholine on the heart of the pithed ratin vivo, pretreated with hexamethonium and/or propranolol, has been demonstrated. Similarly, gallamine was shown to have a significant antiacetylcholine activity on the heart of the spinal cat preparation. The effect of hexamethonium on the cat, however, differed from that on the rat, as in the former it caused a significant decrease in the apparent affinity constant of gallamine. The possible mechanisms whereby this is caused and the clinical implications, should the cat be similar to man in this regard, are discussed.
This antiacetylcholine activity of gallamine on the heart (negative chronotropic response to acetylcholine) fulfils many of the requirements for competitive antagonism. Parallel results were obtained with atropine except on the hexametho-nium-treated cat. Thus, if atropine acts on the acetylcholine receptor in a competitive manner, it is likely that gallamine does also.
Experiments on the isolated guinea pig ileumin vitro have re-demonstrated the remarkable selectivity of the parasympatholytic activity of gallamine with respect to the cardiovascular system and an interesting antihistaminic action which deserves further study.
As the observed anticholinergic actions of gallamine on the heart of both species were obtained with doses necessary for muscle relaxation, it is conceivable that a true atropine-like action may complement any sympathomimetic action of gallamine in producing the tachycardia encountered in clinical practice.
Résumé
On croyait que la triéthiodure de gallamine produisait une tachycardie à cause de son action vagolytique spécifique. Récemment, Brown et Crout ont démontré que la gallamine pouvait produire un effet inotropique et chronotropique accru à cause de la libération de cathécolamines par les nerfs sympathiques cardiaques. En guise ďanalyses plus complètes de ces mécanismes, nous avons fait des expériences sur des rats décérébrés et cordotomisés, sur des chats vivants au cerveau détruit et traités au préalable au propranolol et/ou à ľhexaméthonium pour préciser la nature de ľactivité antiacétylcholine de la gallamine sur le cœur. Les courbes dose-réponse de ľactivité chronotropique négative de ľacétylcholine donnée par voie endoveineuse obtenues après la gallamine par voie endoveineuse et/ou ľatropine confirment ľactivité “atropine-like” de la gallamine réalisant plusieurs des exigences comme antagoniste compétitif. Les affmites constantes apparentes pour ľatropine et la gallamine sont différentes chez le rat et chez le chat. Des études faites sur ľiléon du cobaye confirment la sélectivité cardiovasculaire de ľaction antimuscarinique de la gallamine. Ľantagonisme intéressant de la gallamine par ľhexaméthonium sur le coeur du chat est un exemple ďinteraction des médicaments que nous avons discutée. Cette activité antiacétylcholine de la gallamine s’ajoute, selon toute vraisemblance, à toute libération de cathécolamines pour produire la tachycardie observée en clinique.
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Supported in part by a grant-in-aid from the Ontario Heart Foundation of Canada, grant 3–15, and in part from the Medical Research Council of Canada, grant ma 1216.
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Rathbun, F.J., Hamilton, J.T. Effect of gallamine on cholinergic receptors. Canad. Anaes. Soc. J. 17, 574–590 (1970). https://doi.org/10.1007/BF03004717
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DOI: https://doi.org/10.1007/BF03004717