Pharmacological properties of diacetolol (M&B 16,942), a major metabolite of acebutolol

Diacetolol (M & B 16,942), the major metabolite of the beta-adrenoceptor blocking agent, has been compared pharmacologically with acebutolol. In vitro, the beta-adrenoceptor blocking potency of diacetolol was less than that of acebutolol but its cardioselectivity (atrial relative to tracheal tissue) was greater. In the anaesthetized cat both agents had closely similar beta-adrenoceptor blocking potency and cardioselectivity. Diacetolol had weak intrinsic sympathomimetic activity (ISA), and no significant membrane-stabilizing activity (MSA). It did not restore sinus rhythm to anaesthetized dogs with ouabain-induced arrhythmias but was similar to acebutolol in preventing arrhythmia induced by adrenaline/methylchloroform in anaesthetized cats. It is concluded that, in experimental animals, diacetolol has beta-adrenoceptor blocking properties and ISA similar to the parent compound but differs in its lack of MSA.