Comparison of the angiotensin II antagonist UP269-6 with the angiotensin converting enzyme inhibitor enalapril in normotensive volunteers challenged with angiotensin I

J Cardiovasc Pharmacol. 1995 Jun;25(6):986-93. doi: 10.1097/00005344-199506000-00019.


We assessed the inhibitory effect of UP269-6, a new orally active angiotensin II (ANG II) receptor antagonist, on the pressor action of exogenous ANG I in healthy male volunteers maintained on an unrestricted sodium intake and compared it with that of enalapril. Seven different single doses of UP269-6 ranging from 5 to 180 mg, 20 mg enalapril, or placebo were administered to 16 subjects in a double-blind fashion. The order of placebo and enalapril was randomized, and UP269-6 was given in an ascending dose order. The peak systolic blood pressure (SBP) response to a test dose of ANG I was determined serially before and after oral drug administration by monitoring finger BP by a photoplethysmographic method. No drug-related side effect was observed. There was a dose-dependent inhibition of the SBP response to the ANG I challenge. Doses as low as 40 to 80 mg had blocking effects quite similar to that of enalapril 20 mg. Ten hours after the 20- and 40-mg doses of UP269-6, the SBP response was still attenuated when drug levels no longer were measurable in plasma. UP269-6 also produced a dose-related increase in active renin and ANG II levels at 24 h after drug intake. In these volunteers on unrestricted salt intake, no statistically significant effect on 24-h urinary aldosterone excretion was observed. Based on these preliminary data, the pharmacokinetic drug half-life (t 1/2) was estimated at 4.7 h and the EC50 was estimated at 41 ng/ml. UP269-6 appears to be a well-tolerated, potent, orally active, antagonist of ANG II receptors in men. Doses of 40-80 mg might block the ANG I pressor response as does enalapril 20 mg.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Administration, Oral
  • Adult
  • Aldosterone / urine
  • Analysis of Variance
  • Angiotensin I / administration & dosage
  • Angiotensin I / adverse effects*
  • Angiotensin II / blood
  • Angiotensin Receptor Antagonists*
  • Angiotensin-Converting Enzyme Inhibitors / administration & dosage
  • Angiotensin-Converting Enzyme Inhibitors / pharmacokinetics
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology*
  • Blood Pressure / drug effects*
  • Blood Pressure Determination
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Enalapril / administration & dosage
  • Enalapril / pharmacokinetics
  • Enalapril / pharmacology*
  • Humans
  • Male
  • Plethysmography
  • Pyrimidines / administration & dosage
  • Pyrimidines / pharmacokinetics
  • Pyrimidines / pharmacology*
  • Renin / blood
  • Tetrazoles / administration & dosage
  • Tetrazoles / pharmacokinetics
  • Tetrazoles / pharmacology*


  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Pyrimidines
  • Tetrazoles
  • Angiotensin II
  • UP 269-6
  • Aldosterone
  • Enalapril
  • Angiotensin I
  • Renin