2. Academic Validation
  3. Pharmacology of endothelin receptor antagonists ABT-627, ABT-546, A-182086 and A-192621: ex vivo and in vivo studies

Pharmacology of endothelin receptor antagonists ABT-627, ABT-546, A-182086 and A-192621: ex vivo and in vivo studies

  • Clin Sci (Lond). 2002 Aug;103 Suppl 48:112S-117S. doi: 10.1042/CS103S112S.
Jerry L Wessale 1,  Andrew L Adler,  Eugene I Novosad,  Samuel V Calzadilla,  Brian D Dayton,  Kennan C Marsh,  Martin Winn,  Hwan-Soo Jae,  Thomas W von Geldern,  Terry J Opgenorth,  J Ruth Wu-Wong
Affiliations

Affiliation

  • 1 Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, IL 60064, U.S.A.
PMID: 12193067 DOI: 10.1042/CS103S112S
Abstract

Endothelins (ETs), 21-amino-acid Peptides involved in the pathogenesis of various diseases, bind to ET(A) and ET(B) receptors to initiate their effects. Based on the same core structure, we have developed four small-molecule ET receptor antagonists, ABT-627 (atrasentan), ABT-546, A-182086 and A-192621, which exhibit differences in selectivity for ET(A) and ET(B) receptors. In this report, we compare the efficacy, potency and pharmacokinetic properties of these four antagonists, including potency in inhibiting ET-1- or Sarafotoxin 6c-induced vessel constriction in isolated arteries and efficacy in antagonizing ET-1-, big ET-1- or Sarafotoxin 6c-induced pressor responses in rats.

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