Pharmacodynamic studies in normal volunteers with MDL-899, a new arteriolar vasodilator.
We conducted pharmacodynamic studies with a new vasodilator, MDL-899. Following initial dose-ranging studies we studied eight male normotensive volunteers, each of whom received, orally, 10 mg MDL-899 or placebo in double-blind random order. MDL-899 significantly lowered standing blood pressure, the maximal effect occurring 3-6 h following drug administration. There was a significant increase in heart rate in both supine and standing positions, maximal 6-8 h postdose. Supine plasma noradrenaline concentrations were greater following MDL-899, with the greatest difference present 4 h after drug administration. Plasma renin concentrations were greater following MDL-899. Six of our subjects were also given 10 mg MDL-899 together with 100 mg atenolol, in an additional study. Atenolol increased the hypotensive effect and attenuated the tachycardia following MDL-899 alone. Side effects following MDL-899 administration included headache, lightheadedness, and tachycardia. These were reduced following atenolol coadministration. The haemodynamic profile of MDL-899 suggests that this drug acts as a direct arteriolar vasodilator in man. The observed increase in heart rate is likely mediated by reflex activation of the sympathetic nervous system.
D000293:Adolescent; D000328:Adult; D001262:Atenolol / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D009638:Norepinephrine / Q000097:blood; D011724:Pyridazines / Q000009:adverse effects / Q000494:pharmacology*; D012083:Renin / Q000097:blood; D013997:Time Factors; D014665:Vasodilator Agents / Q000009:adverse effects / Q000494:pharmacology*
D011724:Pyridazines; D014665:Vasodilator Agents; D001262:Atenolol; C038811:mopidralazine; D012083:Renin; D009638:Norepinephrine