IC87201 is an inhibitor of the protein-protein interaction between neuronal nitric oxide synthase (nNOS) and post-synaptic density protein 95 (PSD-95).1 It inhibits the binding of PSD-95 to nNOS (IC50 = 31 ?M). IC87201 inhibits NMDA-induced cGMP production, a marker of PSD-95-dependent NOS activation, in primary rat hippocampal neurons (IC50 = 2.7 ?M). IC87201 (10 ?M) reduces MPP+-induced production of reactive oxygen species (ROS), cytochrome c release, and apoptosis in primary rat cortical neurons.2 In vivo, IC87201 decreases thermal hyperalgesia in mice (ED50 = 0.1 mg/kg), as well as mechanical allodynia in a rat model of neuropathic pain induced by chronic constriction injury (CCI). It also reduces immobility time in the forced swim and tail suspension tests in mice when administered at a dose of 1 mg/kg.3
1.Florio, S.K., Loh, C., Huang, S.M., et al.Disruption of nNOS-PSD95 protein-protein interaction inhibits acute thermal hyperalgesia and chronic mechanical allodynia in rodentsBr. J. Pharmacol.158(2)494-506(2009) 2.Hu, W., Guan, L.-S., Dang, X.-B., et al.Small-molecule inhibitors at the PSD-95/nNOS interface attenuate MPP+-induced neuronal injury through Sirt3 mediated inhibition of mitochondrial dysfunctionNeurochem. Int.7957-64(2014) 3.Doucet, M.V., Levine, H., Dev, K.K., et al.Small-molecule inhibitors at the PSD-95/nNOS interface have antidepressant-like properties in miceNeuropsychopharmacology38(8)1575-1584(2013)