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. 1996 Sep 17;93(19):10477–10482. doi: 10.1073/pnas.93.19.10477

CP-154,526: a potent and selective nonpeptide antagonist of corticotropin releasing factor receptors.

D W Schulz 1, R S Mansbach 1, J Sprouse 1, J P Braselton 1, J Collins 1, M Corman 1, A Dunaiskis 1, S Faraci 1, A W Schmidt 1, T Seeger 1, P Seymour 1, F D Tingley 3rd 1, E N Winston 1, Y L Chen 1, J Heym 1
PMCID: PMC38410  PMID: 8816826

Abstract

Here we describe the properties of CP-154,526, a potent and selective nonpeptide antagonist of corticotropin (ACTH) releasing factor (CRF) receptors. CP-154,526 binds with high affinity to CRF receptors (Ki < 10 nM) and blocks CRF-stimulated adenylate cyclase activity in membranes prepared from rat cortex and pituitary. Systemically administered CP-154,526 antagonizes the stimulatory effects of exogenous CRF on plasma ACTH, locus coeruleus neuronal firing and startle response amplitude. Potential anxiolytic activity of CP-154,526 was revealed in a fearpotentiated startle paradigm. These data are presented in the context of clinical findings, which suggest that CRF is hypersecreted in certain pathological states. We propose that a CRF antagonist such as CP-154,526 could affirm the role of CRF in certain psychiatric diseases and may be of significant value in the treatment of these disorders.

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Selected References

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