Background:

Phosphoramidon Disodium Salt is a potent inhibitor of metalloproteinase [1].

Metalloproteinase is an enzyme whose catalytic mechanism involves a metal. Most metalloproteases require zinc and some require cobalt.

Phosphoramidon Disodium Salt is a potent metalloproteinase inhibitor. In porcine aortic endothelial cells, phosphoramidon (10-4 M) inhibited immunoreactive-endothelin (IR-ET) release by 10-20% and increased IR-CTF levels. These results suggested that phosphoramidon reduced the IR-ET release through affecting the conversion of big ET-1 to ET-l [1]. In cultured endothelial cells, phosphoramidon inhibited the increase of ET-1 and C-terminal fragment (CTF) of big ET-1. However, phosphoramidon increased big ET-1 secretion [2].

In anesthetized rats, phosphoramidon inhibited the hypertensive effect of big ET-1 [2]. In mice, phosphoramidon inhibited big ET-1 induced lethality and increased plasma IR-ET-1 through inhibition of the enzyme that converted big ET-1 to ET-1 [3].

参考文献:
[1].  Ikegawa R, Matsumura Y, Tsukahara Y, et al. Phosphoramidon, a metalloproteinase inhibitor, suppresses the secretion of endothelin-1 from cultured endothelial cells by inhibiting a big endothelin-1 converting enzyme. Biochem Biophys Res Commun, 1990, 171(2): 669-675.
[2].  Matsumura Y, Ikegawa R, Hisaki K, et al. Conversion of big endothelin-1 to endothelin-1 by phosphoramidon-sensitive metalloproteinase derived from aortic endothelial cells. J Cardiovasc Pharmacol, 1991, 17 Suppl 7: S65-7.
[3].  Matsuura A, Okumura H, Ashizawa N, et al. Big endothelin-1-induced sudden death is inhibited by phosphoramidon in mice. Life Sci, 1992, 50(21): 1631-1638.