Enalaprilat (hydrate)

Enalaprilat (dihydrate) (MK-422) is an angiotensin-converting enzyme (ACE) inhibitor with IC50 of 1.94 nM.

Enalaprilat has high affinity for human endothelial ACE with IC50 of 1.94 nM in vitro binding assay by displacing a saturating concentration of [125I]351A, a radiolabeled lisinopril analogue from ACE binding sites, and shows bradykinin/angiotensin I selectivity ratio of 1.00 calculated from double displacement experiments[1]. Enalaprilat attenuates the IGF-I induced neonatal rat cardiac fibroblast growth (30% reduction) in a concentration-dependent fashion, with IC50 of 90 mM[2].

Administration of Enalaprilat induces a significant reduction of MAP at 70 minutes compared with the placebo group during haemorrhagic shock in rats, and results in a 50% reduction of CO, a general tendency of EB extravasation which is significant in the kidney and lungs, and a significant increase in ileal EB extravasation (53%)[3].

References:
[1]. Ceconi, C., et al., Angiotensin-converting enzyme (ACE) inhibitors have different selectivity for bradykinin binding sites of human somatic ACE. Eur J Pharmacol, 2007. 577(1-3): p. 1-6.
[2]. van Eickels, M., H. Vetter, and C. Grohe, Angiotensin-converting enzyme (ACE) inhibition attenuates insulin-like growth factor-I (IGF-I) induced cardiac fibroblast proliferation. Br J Pharmacol, 2000. 131(8): p. 1592-6.
[3]. Schumacher, J., et al., Effects of candesartan and enalaprilat on the organ-specific microvascular permeability during haemorrhagic shock in rats. Br J Anaesth, 2006. 96(4): p. 437-43.