Antihypertensive and adrenoceptor blocking properties of new sulfonamide-substituted phenylethylamines

Studies on the structure-activity relationship using 9 new 3-sulfamoylphenylethylamines revealed that YM-09538, YM-09649 and YM-09686 were competitive antagonists at both beta- and post-synaptic alpha-receptors. The following order of adrenoceptor blocking activities was obtained : propranolol greater than labetalol greater than YM-09538 greater than YM-09649 greater than YM-09686 for beta-receptors and prazosin greater than YM-09686 greater than YM-09649 greater than YM-09538 greater than phentolamine greater than labetalol for postsynaptic alpha-receptors. In contrast to phentolamine, three YM-compounds showed low affinities for presynaptic alpha-receptors similar to prazosin and labetalol. These antagonists except propranolol effectively lowered blood pressure in conscious SHR and their relative effectiveness parallels the postsynaptic alpha-blocking activity. At hypotensive doses, phentolamine markedly and prazosin, YM-09686 and YM-09649 moderately increased heart rate, whereas YM-09538 and labetalol failed to increase the rate. These results indicate that the postsynaptic alpha-blocking activity of YM-compounds contributes to their hypotensive activities and that both beta-blocking and low presynaptic alpha-blocking activities contribute to attenuation of the tachycardia.