Pharmacological profile of ME3221, a novel angiotensin II receptor antagonist

Eur J Pharmacol. 1995 Feb 14;274(1-3):201-11. doi: 10.1016/0014-2999(94)00740-x.

Abstract

The pharmacological profile of a new surmountable angiotensin AT1 receptor antagonist, ME3221, 3-methoxy-2,6-dimethyl-4-[[2'-(1H-tetrazol-5-yl)-1,1'-biphenyl-4- yl]methoxy]pyridine, was studied in several animal models, and was compared with that of losartan. EF2831, 3-hydroxy-2,6-dimethyl-4-[[2'-(1H-tetrazol-5-yl)-1,1'-biphenyl-4- yl]methoxy]pyridine, a metabolite of ME3221, is also a surmountable angiotensin AT1 receptor antagonist, whose potency was 1/30 that of ME3221 in vitro, but equal to or 1/3 of that of ME3221 in in vivo experiments. In rats and marmosets, ME3221 antagonized angiotensin II-induced pressor responses, but did not affect bradykinin-induced depressor responses. ME3221 lowered the blood pressure in renal hypertensive rats and spontaneously hypertensive rats (SHR), and its ED25 value was 3 times that of losartan. Repeated administration of ME3221 to SHR had a stable and long-lasting antihypertensive effect without influencing heart rate. Thus ME3221, like losartan, may be useful in the treatment of renal and essential hypertension.

MeSH terms

  • Angiotensin II / antagonists & inhibitors*
  • Angiotensin Receptor Antagonists*
  • Animals
  • Antihypertensive Agents / administration & dosage
  • Antihypertensive Agents / pharmacology*
  • Antihypertensive Agents / therapeutic use
  • Aorta, Thoracic / drug effects
  • Aorta, Thoracic / metabolism
  • Biphenyl Compounds / administration & dosage
  • Biphenyl Compounds / pharmacology*
  • Biphenyl Compounds / therapeutic use
  • Blood Pressure / drug effects
  • Bradykinin / pharmacology
  • Callithrix
  • Disease Models, Animal
  • Drug Evaluation
  • Female
  • Femoral Artery / drug effects
  • Femoral Artery / metabolism
  • Heart Rate / drug effects
  • Hypertension, Renal / drug therapy
  • Imidazoles / administration & dosage
  • Imidazoles / pharmacology*
  • Imidazoles / therapeutic use
  • Losartan
  • Male
  • Rabbits
  • Rats
  • Rats, Inbred SHR
  • Rats, Sprague-Dawley
  • Species Specificity
  • Tetrazoles / administration & dosage
  • Tetrazoles / pharmacology*
  • Tetrazoles / therapeutic use

Substances

  • Angiotensin Receptor Antagonists
  • Antihypertensive Agents
  • Biphenyl Compounds
  • Imidazoles
  • ME 3221
  • Tetrazoles
  • Angiotensin II
  • losartan carboxylic acid
  • Losartan
  • Bradykinin