Pharmacology of SC‐52458, an Orally Active, Nonpeptide Angiotensin AT1 Receptor Antagonist

  title={Pharmacology of SC‐52458, an Orally Active, Nonpeptide Angiotensin AT1 Receptor Antagonist},
  author={Gillian M. Olins and Valerie M. Corpus and Susan T. Chen and Ellen G. Mcmahon and Maria A. Palomo and D. E. Mcgraw and Glenn J. Smits and Christopher L Null and Melanie A. Brown and S E Bittner and John P. Koepke and Delores J. Blehm and Joseph R. Schuh and Chris J. Baierl and Robert E. Schmidt and Chyung S. Cook and David B. Reitz and Mark Andrew Penick and Robert E. Manning and Edward H. Blaine},
  journal={Journal of Cardiovascular Pharmacology},
Summary We describe the pharmacologic properties of SC-52458, 5-[(3,5-dibutyl-1H-1,2,4-triazol-1-yl)methyl]-2-[2-(1H-tetrazol-5-ylphenyl)]pyridine, a novel nonpeptide angiotensin II (AH) receptor antagonist. SC-52458 was a potent inhibitor of [125I]AII binding to AT, receptors in rat adrenal cortex and uterine smooth muscle membranes (IC50 values of 2.8 and 6.9 nM, respectively). Contraction of rabbit aortic rings by AII was antagonized by SC-52458 in a competitive and reversible manner (pA2 of… 

Effects of SC-52458, an angiotensin AT1 receptor antagonist, in the dog.

Antihypertensive effect of chronic KT3-671, a structurally new nonpeptide angiotensin AT1-receptor antagonist, in stroke-prone spontaneously hypertensive rats.

Results suggest that KT3-671 is a potentially useful antihypertensive drug and reduced the severity of the pathological changes in the kidney.

Antihypertensive activity and pharmacokinetics of KD3-671, a nonpeptide AT1-receptor antagonist, in renal hypertensive dogs.

The antihypertensive activity and pharmacokinetic parameters of KD3-671 were investigated in renal hypertensive dogs with normal or high plasma renin activity and it is suggested that the drug may be useful for the treatment of hypertension.

Up-regulation of angiotensin type 2 receptor mRNA by angiotensin II in rat cortical cells.

The present experiment demonstrates that the exposure of angiotensin II (AII) produced an up-regulation of the AT2 receptor mRNA level in rat cortical cells and suggests that the AT1 receptor mRNA expression by AII is regulated by the activity of serine/threonine phosphatase in the cortical neurons.

Hypotensive effect of ZD7155, an angiotensin II receptor antagonist, parallels receptor occupancy in two‐kidney, one‐clip Goldblatt hypertensive rats

ZD7155 is a potent antihypertensive agent in two-kidney, one-clip Goldblatt hypertensive rats and this effect is accompanied by sustained inhibition of tissue angiotensin II binding.

Possible involvement of calcium-calmodulin pathways in the positive chronotropic response to angiotensin II on the canine cardiac sympathetic ganglia.

Results suggest that Ang II stimulates the ganglionic transmission at postsynaptic sites via the activation of AT1 receptor coupled to either activation of phospholipase C, phosphoinositide hydrolysis and subsequent increase in intracellular Ca2+ and activation of protein kinase C and Ca2/CaM kinase II, although this ganglionics stimulation seems to involve the protein kinases-dependent increase of amiloride-sensitive Na+ inflow.

The angiotensin II type 1 receptor antagonists. A new class of antihypertensive drugs.

These drugs antagonize AII-induced biologic actions, including smooth-muscle contraction, sympathetic pressor mechanisms, and aldosterone release, and are the newest addition to the therapeutic armamentarium for the treatment of hypertensive diseases.

Cardiac hypertrophy-related gene expression in spontaneously hypertensive rats: crucial role of angiotensin AT1 receptor.

The expression of skeletal alpha-actin and ANP was selectively enhanced in the heart of vehicle-treated SHR compared with Wistar-Kyoto rats (WKY), thereby suggesting that the phenotypic modulation of myocytes occurred at the early stage of hypertension.