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

被引:329
作者
Schulz, DW
Mansbach, RS
Sprouse, J
Braselton, JP
Collins, J
Corman, M
Dunaiskis, A
Faraci, S
Schmidt, AW
Seeger, T
Seymour, P
Tingley, FD
Winston, EN
Chen, YL
Heym, J
机构
[1] Department of Neuroscience, Pfizer Central Research, Groton
关键词
D O I
10.1073/pnas.93.19.10477
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 (K-i < 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 fear-potentiated 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.
引用
收藏
页码:10477 / 10482
页数:6
相关论文
共 48 条