R121919 (NBI30775)

R121919 is a potent small-molecule CRF1 receptor antagonist with a Ki of 2 to 5 nM for the CRF1 receptor and over 1000-fold weaker activity at the CRF2 receptor, CRF-binding protein, or 70 other receptor types.

R121919 is a potent small-molecule CRF1 receptor antagonistwith high affinity for the CRF1 receptor (Ki=2-5 nM) and over 1000-fold weaker activity at the CRF2 receptor, CRF-binding protein, or 70 other receptor types[1].

R121919 reduces measures of both anxiety and depression in the depressed patients. R121919 dose dependently decreases adrenocorticopin hormone and corticosterone responses to restraint stress in rats. Peak plasma adrenocorticopin hormone and corticosterone concentrations at a dose of 10 mg/kg R121919 are 9 and 25%, respectively[1]. R121919 reduces levels of anxiety in mice with a steep dose-response curve. Molecules such as GR, MR, BAG-1 and AP-1 have been identified as some of the drug's intracellular targets[2].

[1]. Gutman DA, et al. The corticotropin-releasing factor1 receptor antagonist R121919 attenuates the behavioral and endocrine responses to stress. J Pharmacol Exp Ther. 2003 Feb;304(2):874-80. [2]. Post A, et al. Identification of molecules potentially involved in mediating the in vivo actions of the corticotropin-releasing hormone receptor 1 antagonist, NBI30775 (R121919). Psychopharmacology (Berl). 2005 Jun;180(1):150-8.