Thiorphan

Thiorphan is a selective neprilysin (NEP) inhibitor with an IC₅₀ of 6.9 nM. Thiorphan competitively binds to NEP and blocks its activity, preventing the degradation of neuropeptides such as substance P (SP) and neurokinin NKA. In the field of neonatal brain injury research, Thiorphan can increase the levels of SP and NKA, activate NK1 and NK2 receptors and downstream transduction pathways, and inhibit excessive activation of NMDA receptors. Thus, Thiorphan can protect neocortical neurons from excitotoxic cell death. Thiorphan may also inhibit NEP from enhancing bronchoconstriction and can be used in the study of respiratory diseases^[1][2][3]. In Vitro:Thiorphan (5 μM; 12 h) protects neurons from excitotoxic stimulation and blocks the neurodegradation of substance P (10 μM) in primary neuronal cultures exposed to 300 μM NMDA^[3]. In Vivo:Thiorphan (25 μg intracerebral or 50 mg/kg intraperitoneal; given as a single dose after ibotenic acid injection) reduces cortical damage and cortical caspase-3 cleavage in a mouse model of excitotoxic brain injury induced by ibotenic acid (HY-N2311), and this neuroprotective effect is still observed 12 hours after injury. This effect can be mimicked by substance P and neurokinin A, and is inhibited by NK1 and NK2 receptor blockers[3].