Thiorphan-d5

Biological Activity

Thiorphan-d5 is intended for use as an internal standard for the quantification of thiorphan by GC- or LC-MS. Thiorphan is an inhibitor of neprilysin (NEP; IC50 = 0.007 μM).1 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).1,2 Thiorphan (10 μM) increases bradykinin-induced relaxation of isolated porcine coronary artery rings precontracted with potassium chloride under hypoxic, but not normoxic, conditions.3 Thiorphan reduces increases in gastric acid output induced by pentagastrin 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.4 Thiorphan (2 mg/ml, i.c.v.) increases cortical levels of insoluble amyloid-β (1-40) (Aβ40) and decreases time spent in the platform quadrant in the Morris water maze, indicating impaired reference memory, in rats.5

References

1.Whyteside, A.R., and Turner, A.J.Human neprilysin-2 (NEP2) and NEP display distinct subcellular localisations and substrate preferencesFEBS Lett.582(16)2382-2386(2008) 2.Inguimbert, N., Coric, P., Poras, H., et al.Toward an optimal joint recognition of the S1' subsites of endothelin converting enzyme-1 (ECE-1), angiotensin converting enzyme (ACE), and neutral endopeptidase (NEP)J. Med. Chem.45(7)1477-1486(2002) 3.Krassói, I., Pataricza, J., and Papp, J.G.Thiorphan enhances bradykinin-induced vascular relaxation in hypoxic/hyperkalaemic porcine coronary arteryJ. Pharm. Pharmacol.55(3)339-345(2003) 4.Chicau-Chover, M., Dubrasquet, M., Chariot, J., et al.Thiorphan and acetorphan inhibit gastric secretion by a central, non-opioid mechanism in the ratEur. J. Pharmacol.154(3)247-254(1998) 5.Mouri, A., Zou, L.B., Iwata, N., et al.Inhibition of neprilysin by thiorphan (i.c.v.) causes an accumulation of amyloid β and impairment of learning and memoryBehav. Brain Res.168(1)83-91(2006)

Raw materials

Preparation Products