INVITRO STUDIES ON THE PHARMACOLOGICAL PROPERTIES OF DIACETOLOL, THE MAJOR METABOLITE OF ACEBUTOLOL IN MAN

  • 1 January 1985
    • journal article
    • research article
    • Vol. 273  (1) , 4-17
Abstract
The cardioselectivity and specificity of diacetolol, the major metabolite of the .beta.-adrenoceptor blocking drug acebutolol, was studied in the isolated right atrium of the guinea-pig and rat and the papillary muscle and trachea of the guinea-pig. The .beta.-adrenoceptor blocking potency of diacetolol was about 10 times lower than that of acebutolol. Diacetolol was a more effective isoprenaline antagonist in the heart than in the trachea, thus showing relative cardioselectivity. The high water solubility of diacetolol and acebutolol led to a much faster disappearance of the .beta.-blockade after washout than the blockade by the lipid soluble agents propranolol and penbutolol. Diacetolol had a weak intrinsic sympathomimetic activity. Cardiac depressant effects, e.g. decrease of maximum upstroke velocity and duration of the action potential and reduction in force of contraction, occurred with concentrations 100-1000 times higher than those needed for .beta.-blockade, thus indicating relative specificity.