SCH 42495

SCH 42495 is an orally active neutral metalloendopeptidase (NEP) inhibitor with antihypertensive effect. SCH 42495 is the orally active ethylester prodrug of SCH 42354[1].

Research Areas >> Cardiovascular Disease

Signaling Pathways >> Metabolic Enzyme/Protease >> Neprilysin

NEP[1]

SCH 42354 selectively inhibits hydrolysis of leu-enkephalin and ANF (IC50 of 8.3 and 10.0 nM, respectively) in vitro[1].

SCH 42495 (30 mg/kg; oral gavage; twice daily) causes a significant reduction in the pulmonary vascular remodelling and ventricular hypertrophy in hypoxic rats after 10 days[2]. Treatment with SCH 42495 (30 mg/kg; oral gavage; twice daily) leads to a decrease in cardiovascular remodelling secondary to chronic hypoxia in rats[2]. SCH 42495 (oral doses of 1, 3, or 10 mg/kg) produces significant reductions in blood pressure in DOCA-N a hypertensive rats of 22±6, 43±7, and 62±12 mm Hg, respectively[1]. Animal Model: Hypoxic rats[2] Dosage: 30 mg/kg Administration: Oral gavage; twice daily for 10 days Result: Caused a significant reduction in the pulmonary vascular remodelling and ventricular hypertrophy. Led to a decrease in cardiovascular remodelling secondary to chronic hypoxia.

[1]. Watkins RW, et al. Atrial natriuretic factor potentiating and hemodynamic effects of SCH 42495, a new, neutral metalloendopeptidase inhibitor. Am J Hypertens. 1993 May;6(5 Pt 1):357-68.

[2]. Thompson JS, et al. Effects of the neutral endopeptidase inhibitor, SCH 42495, on the cardiovascular remodelling secondary to chronic hypoxia in rats. Clin Sci (Lond). 1994 Jul;87(1):109-14.