Study on some selective beta-adrenoreceptor blocking effects of 1-(4-nitrophenyl)-1-hydroxy-2-methyl isoproylaminoethane (alpha-methyl INPEA).

1. The effect of methyl substitution in the alpha-carbon position of the ethanolamine side chain of INPEA was investigated on its beta-adrenoreceptor blocking activity in the isolated turtle heart and anaesthetized cats.2. In the turtle heart preparation, the pA(2) value for erythro-alpha-methyl INPEA was 5.3, as compared with 6.9 for INPEA, while threo-alpha-methyl INPEA was extremely weak and its pA(2) value could not be determined.3. In the intact cat experiments, alpha-methyl INPEA produced a competitive blockade of the peripheral vasodilator effect of isoprenaline in doses ranging from 5 to 20 mg/kg. However, this agent had a minimal effect on the cardiac stimulant effect of the catecholamine.4. These results are consistent with the hypothesis that the beta-adrenoreceptors comprise a family of nonhomogeneous receptors and a selective blockade of only some, but not all, responses mediated through their activation can be achieved by specific molecular modification of the beta-adrenoreceptor blocking agents.