Pharmacological studies on the intrinsic sympathomimetic activity of the beta-adrenoceptor antagonist mepindolol.
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.
Beckmann
R
R
Müller
B
B
Schröder
G
G
Stock
G
G
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000758:Anesthesia; D000818:Animals; D006321:Heart / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D010869:Pindolol / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D013566:Sympathomimetics
D000319:Adrenergic beta-Antagonists; D013566:Sympathomimetics; C015340:mepindolol; D010869:Pindolol; D007545:Isoproterenol