AMINOACYL DERIVATIVES OF DOPAMINE AS ORALLY EFFECTIVE RENAL VASODILATORS

Publisher Summary This chapter elaborates the aminoacyl derivatives of dopamine as orally effective renal vasodilators. The intra-duodenal administration of 12 or 24 mg/kg of ABBOTT-41596 to anesthetized dogs produced a significant increase in renal blood flow (RBF) for 155 and 172 min, with a peak increase of 31 and 44%, respectively. RBF was measured by an electromagnetic flow probe around the renal artery. Plasma samples taken from these animals demonstrated the presence of both intact amide and markedly increased concentrations of dopamine. The drug produced only minimal systemic hemodynamic effects at the lower dose and at the higher dose, pharmacological responses characteristic of both α and β-adrenoreceptor stimulation were seen also. Pretreatment with both phenoxybenzamine and propranolol increased RBF by 55–75% at doses of 12–24 mg/kg/i.d., suggesting that the renal vasodilator effect is independent of α or β-adrenoreceptor stimulation. In Rhesus monkeys,12 and 24 mg/kg/i.d. of ABBOTT-41596 increased RBF by an average of 25, and 37%, respectively, with an onset time of 3–5 min, and duration greater than 30 min.