| Literature DB >> 11168542 |
M E Keck1, T Welt, A Wigger, U Renner, M Engelmann, F Holsboer, R Landgraf.
Abstract
Hyperactivity of central corticotropin-releasing hormone (CRH) circuits appears to contribute to the symptomatology of affective and anxiety disorders and therefore CRH receptor antagonists have attracted attention as potential therapeutic agents. R121919, a novel high-affinity nonpeptide CRH(1) receptor antagonist, displaced (125)I-oCRH in rat pituitary, cortex and amygdala, but not in choroid plexus or cerebral blood vessels in vitro and in vivo, which is consistent with CRH(1) receptor antagonism. In vivo, R121919 significantly inhibited stress-induced corticotropin release in rats selectively bred for high- and low-anxiety-related behaviour but displayed anxiolytic effects in high-anxiety rats only. These data, corroborated by ex vivo receptor occupancy studies, suggest that this animal model is appropriate for the evaluation of CRH(1) receptor antagonists and that compounds such as R121919 will be beneficial whenever the central stress hormone system is hyperactive.Entities:
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Year: 2001 PMID： 11168542 DOI： 10.1046/j.0953-816x.2000.01383.x
Source DB: PubMed Journal: Eur J Neurosci ISSN： 0953-816X Impact factor: 3.386