Thiorphan

Thiorphan is an inhibitor of neprilysin (NEP; IC50 = 0.007 µM).{24072} It selectivity inhibits NEP over NEP2 (IC50 = 22 µM), as well as angiotensin-converting enzyme (ACE) and endothelin-converting enzyme 1 (ECE1; Kis = >0.1 and >10 µM, respectively, in cell-free assays).{24072,25518} Thiorphan (10 µM) increases bradykinin-induced relaxation of isolated porcine coronary artery rings precontracted with potassium chloride under hypoxic, but not normoxic, conditions.{52118} Thiorphan reduces increases in gastric acid output induced by pentagastrin (Item No. 28546) by 64% in rats when administered intracerebroventricularly at a dose of 50 µg, but not when administered intravenously at doses of 1.7 and 17 mg/kg.{52119} Thiorphan (2 mg/ml, i.c.v.) increases cortical levels of insoluble amyloid-? (1-40) (A?40) and decreases time spent in the platform quadrant in the Morris water maze, indicating impaired reference memory, in rats.{52120}