Background:

IC50: 1.7, 3.9, and 3.9 μM for nNOS (rat), eNOS (bovine), and iNOS (mouse), respectively

L-NIO is a NOS inhibitor.

Nitric oxide synthases (NOSs) are enzymes that catalyze the production of nitric oxide (NO) from L-arginine. NO is an important cellular signaling molecule and helps modulate vascular tone, airway tone, insulin secretion, and peristalsis. NO is involved in angiogenesis and neural development.

In vitro: Three analogues of L-arginine were characterized as inhibitors of endothelial NO synthase by measuring their effect on the endothelial NO synthase from porcine aortae. It was found that L-NMMA, L-NIO and L-NAME could cause concentration-dependent inhibition of the Ca2+-dependent endothelial NO synthase [1].

In vivo: In rats, L-NMMA, L-NIO and L-NAME could induce a dose-dependent increase in mean systemic arterial blood pressure accompanied by bradycardia. Moreover, L-NMMA, L-NIO and L-NAME at i.v. 100 mg/kg significantly inhibited the hypotensive responses to ACh and bradykinin. The increase in blood pressure and bradycardia produced by these compounds were able to be reversed by L-arginine in a dose-dependent manner. Moreover, all of these effects were enantiomer specific [1].

Clinical trial: So far, no clinical study has been conducted.

Reference:
[1] D.  D. Rees, R. M. J. Palmer, R. Schulz, et al. Characterization of three inhibitors of endothelial nitric oxide synthase in vitro and in vivo. British Journal of Pharmacology 101, 746-752 (1990).