Antiarrhythmic and electrophysiological effects of ICS 205-930, an antagonist of 5-hydroxytryptamine at peripheral receptors

F. M. Williams, A. L. Rothaul, K. A. Kane, J. Parratt

Research output: Contribution to journalArticle

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Abstract

We assessed the antiarrhythmic activity of ICS 205-930 [(3α-tropanyl)-1H -indole-3-carboxylic acid ester], a selective antagonist at neuronal 5-hydroxytryptamine M-receptors, against the arrhythmias that occur following occlusion of the left main coronary artery in anaesthetised rats and subsequent release (reperfusion). The incidence of reperfusion-induced ventricular fibrillation and ventricular tachycardia was significantly reduced by pretreatment with ICS 205-930 (0.3 and 1.0 mg kg-1 i.v. and 10 and 30 mg kg-1 p.o.). The arrhythmias that occurred during 30 min of coronary artery occlusion were also less severe in animals given ICS 205-930 (1.0 and 5.0 mg kg-1 i.v.). Arterial blood pressure was not altered by the drug, and heart rate was only slightly reduced by the highest intravenous dose. In vitro, ICS 205-930 reduced the maximum rate of rise of phase 0 of normal sheep Purkinje fibre action potentials in concentrations from 0.5 to 5.0 mg L-1. Action potentials depressed by supervision with a physiological salt solution modified to mimic the conditions occurring during mild ischaemia were similarly affected by ICS 205-930. The highest drug concentration studied under these conditions was 1.5 mg L-1 since, in combination with the modified physiological salt solution, this rendered some of the Purkinje fibres inexcitable. These results indicate that ICS 205-930 possesses marked antiarrhythmic activity against ischaemia-induced arrhythmias in anaesthetised rats and that a direct electrophysiological effect of the drug may, at least in part, underlie its protective action.

Original languageEnglish
Pages (from-to)550-555
Number of pages6
JournalJournal of Cardiovascular Pharmacology
Volume7
Issue number3
Publication statusPublished - 1985

Fingerprint

tropisetron
Serotonin Antagonists
Purkinje Fibers
Cardiac Arrhythmias
Action Potentials
Reperfusion
Coronary Vessels
Ischemia
Salts
Pharmaceutical Preparations
Serotonin Receptors
Coronary Occlusion
Ventricular Fibrillation
Ventricular Tachycardia
Sheep
Arterial Pressure
Esters
Heart Rate

Keywords

  • 5-HT antagonist
  • Electrophysiology
  • ICS 205-930
  • Ischaemia-induced cardiac arrhythmias

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Pharmacology

Cite this

Antiarrhythmic and electrophysiological effects of ICS 205-930, an antagonist of 5-hydroxytryptamine at peripheral receptors. / Williams, F. M.; Rothaul, A. L.; Kane, K. A.; Parratt, J.

In: Journal of Cardiovascular Pharmacology, Vol. 7, No. 3, 1985, p. 550-555.

Research output: Contribution to journalArticle

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