Selective alpha 2-adrenoceptor agonist activity of the novel inotropic agent, ASL-7022: comparison with dobutamine

ASL-7022 is a novel inotropic agent capable of increasing the force of myocardial contraction at doses which produce little effect on heart rate. The inotropic selectivity of ASL-7022, like that of dobutamine, has been proposed to result, in part, from agonist activity at alpha-adrenoceptors. Following beta-adrenoceptor blockade, ASL-7022 and dobutamine increase diastolic blood pressure in pithed rat, with both compounds being equal in potency. The pressor activity of ASL-7022 was selectively antagonized by yohimbine (1 mg/kg i.v.) and was unaffected by prazosin (0.1 mg/kg i.v.), whereas the converse was true for dobutamine. These results indicate that the pressor effects of ASL-7022 and dobutamine are mediated by different populations of postjunctional vascular alpha-adrenoceptors in pithed rat, with ASL-7022 selectively stimulating alpha 2-adrenoceptors and dobutamine selectively activating alpha 1-adrenoceptors.