FIG. 3.

VAS203 treatment against brain traumatic injury. (A) NADPH donates electrons to the reductase domain of NOS. They are transferred via FAD and FMN to the oxygenase domain where they reduce heme-bound oxygen and an intermediate role of BH4. Activated oxygen oxidizes a guanidine nitrogen of l-arginine to produce NO and l-citrulline (1a). VAS203 is an analog of the physiological NOS cofactor tetrahydrobiopterin, which enables blockade of NOS activity. VAS203 exhibits more suitable properties than other classical arginine NOS inhibitors (i.e., L-N⁶-Nitroarginine methyl ester [L-NAME]). (B) VAS203-treated patients significantly reduced the therapeutic intensity level after a 6-day observation period. (C) The median level in the extended Glasgow Outcome Score after 6 months was 1.5 score points higher under VAS203 treatment compared with placebo (133). NOS, nitric oxide synthase. *Statistically significant difference between VAS203 (30 mg/kg) treatment and TL-placebo