3-[6-(Dimethylamino)-4-methyl-3-pyridinyl]-2,5-dimethyl-N,N-dipropylpyrazolo[1,5-a]pyrimidin-7-amine, is a potent and Orally active Corticotropin-Releasing factor 1 receptor antagonists, which is hown to reduce negative emotional symptoms of acute and protracted alcohol withdrawal, and thus used for the treatment of alcoholism.
R121919 (NBI 30775) is a brain-penetrant, orally available high-affinity corticotropin-releasing factor/hormone (CRF or CRH) receptor 1 (CRF1, CRF-R1, CRFR-1, CRH-R1, CRHR-1) antagonist (Ki = 3.5 nM against sauvagine for binding hCRFR1-expressing HEK293 cells; IC50 = 20 nM/CRF-stimulated ACTH release from r at anterior pituitary cells & IC50 = 80 nM/CRF-stimulated cAMP production in hCRFR1-expressing HEK293 cells) without affinity toward CRFR2. In addition to its antistress efficacy in various r at anxiety models (0.63-20 mg/kg p.o.), R121919 also demonstrates therapeutic efficacy and long-term safety in Alzheimerμs disease (AD) mice (20 mg/kg/day s.c.) in vivo.
