Darusentan (Abbott Laboratories).
Abbott (formerly Knoll) is developing darusentan, an endothelin A antagonist, as a potential treatment for congestive heart failure (CHF) [398274]. The compound entered phase II trials in December 1998 [310187]. In a model of monocrotaline-induced pulmonary hypertension, darusentan (50 mg/kg/day), significantly reduced right ventricular systolic pressure, and in a canine model of CHF chronic treatment for 2 weeks significantly reduced left ventricular end diastolic pressure, mean pulmonary artery pressure, and right atrial pressure. Darusentan is a selective antagonist in vitro (ET(A): K(i) = 1.4 nM; ET(B): K(i) = 184 nM) [339872].
Lip
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Haemostasis Thrombosis and Vascular Biology Unit, University Department of Medicine City Hospital, Birmingham, B18 7QH, UK. g.y.h.lip@bham.ac.uk