Pharmacological studies on the intrinsic sympathomimetic activity of the beta-adrenoceptor antagonist mepindolol

Arzneimittelforschung. 1986 May;36(5):811-3.

Abstract

1-Isopropylamino-3-(2-methyl-4-indolyloxy)-2-propanol (mepindolol, Corindolan) is a beta-adrenoceptor antagonist with significant intrinsic sympathomimetic activity (ISA): positive chronotropic effects in atria of the rat amount to 24% of those elicited by the full agonist isoprenaline. Relaxant effects in blood vessels approach 50% of those of isoprenaline. This vasorelaxant effect is completely blocked by the specific beta 2-adrenoceptor antagonist ICI 118 551 (erythro-dl-1-(7-methylindan-4-yloxy)-3-isopropylaminobut an-2-ol), suggesting that the vasodilatory effects of mepindolol are elicited by stimulation of vascular beta 2-adrenoceptors. In the anaesthetized cat mepindolol acutely lowers arterial blood pressure by reducing total peripheral resistance without exhibiting significant cardiodepressant action, whereas propranolol, lacking ISA, lowers blood pressure by a marked reduction of cardiac output and left ventricular contractility, however, total peripheral resistance is significantly increased.

MeSH terms

  • Adrenergic beta-Antagonists / pharmacology*
  • Anesthesia
  • Animals
  • Heart / drug effects
  • Hemodynamics / drug effects*
  • In Vitro Techniques
  • Isoproterenol / pharmacology
  • Male
  • Muscle Relaxation / drug effects
  • Muscle, Smooth, Vascular / drug effects
  • Pindolol / analogs & derivatives*
  • Pindolol / pharmacology
  • Rats
  • Sympathomimetics*

Substances

  • Adrenergic beta-Antagonists
  • Sympathomimetics
  • mepindolol
  • Pindolol
  • Isoproterenol