CP 376,395 is an antagonist of corticotropin-releasing factor (CRF) receptor 1 (CRF1; IC50 = 5.1 nM).1 It inhibits adenylate cyclase activity stimulated by ovine CRF in rat cerebral cortex and at human CRF1 receptors. CP 376,395 (17.8 mg/kg) inhibits CRF-induced increases in the acoustic startle response in rats. It increases the percentage of open arm entries and time spent in the open arms of the elevated plus maze in mice when administered via intramedial prefrontal cortical injection at doses of 1.5 and 3 nmol.2 CP 376,395 (10 mg/kg) reduces ethanol consumption in rats trained on an intermittent access schedule.3 It increases pulmonary ventilation in rats under normocapnic and hypercapnic conditions when injected into the locus coeruleus at a dose of 5 nmol/0.1 μl.4
1.Chen, Y.L., Obach, R.S., Braselton, J., et al.2-Aryloxy-4-alkylaminopyridines: Discovery of novel corticotropin-releasing factor 1 antagonistsJ. Med. Chem.51(5)1385-1392(2008) 2.Miguel, T.T., Gomes, K.S., and Nunes-de-Souza, R.L.Tonic modulation of anxiety-like behavior by corticotropin-releasing factor (CRF) type 1 receptor (CRF1) within the medial prefrontal cortex (mPFC) in male mice: Role of protein kinase A (PKA)Horm. Behav.66(2)247-256(2014) 3.Simms, J.A., Nielsen, C.K., Li, R., et al.Intermittent access ethanol consumption dysregulates CRF function in the hypothalamus and is attenuated by the CRF-R1 antagonist, CP-376395Addict. Biol.19(4)606-611(2014) 4.Incheglu, J.M., Bicego, K.C., and Gargaglioni, L.H.Corticotropin-releasing factor in the locus coeruleus as a modulator of ventilation in ratsRespir. Physiol. Neurobiol.23373-80(2016)