SCH 10595, AN EFFECTIVE DOPAMINE--HYDROXYLASE INHIBITOR AND A HYPOTENSIVE AGENT

¹ Departments of Biochemistry and Pharmacology, Schering Corporation, Bloomfield, New Jersey

The dopamine--hydroxylase inihibitory activity of Sch 10595 [5-n-butyl)-picolinamide] has been determined by measuring the biosynthesis of ¹⁴C-norepinephrine (NE) after ¹⁴C-dopamine administration and also by measuring the endogenous catecholamine levels. Sch 10595 inhibited ¹⁴C-NE biosynthesis in the heart, spleen and brain but had no effect on total tissue radioactivity levels. Sch 10595 also lowered the endogenous NE tissue levels while increasing endogenous dopamine levels above control. The compound was found to lower blood pressure effectively in deoxycorticosterone acetate-hypertensive rats over a wide range od doses (30-300 mg/kg). The durations of this effect and the degree of blood pressure reduction were dose related. The blood pressure-lowering effect was well correlated with the reduction of endogenous NE levels in sympathetically innervated tissues.