- 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.
Clinical science (London, England : 1979) (2002-08-24)
Jerry L Wessale, 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
PMID12193067
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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