Endothelins (ETs), 21-amino-acid peptides involved in the pathogenesis of various diseases, bind to ETA and ETB 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 ETA and ETB 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.
Pharmacology of endothelin receptor antagonists ABT-627, ABT-546, A-182086 and A-192621: ex vivo and in vivo studies
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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; Pharmacology of endothelin receptor antagonists ABT-627, ABT-546, A-182086 and A-192621: ex vivo and in vivo studies. Clin Sci (Lond) 1 September 2002; 103 (s2002): 112S–117S. doi: https://doi.org/10.1042/CS103S112S
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