Corticotropin-releasing factor antagonists: Therapeutic potential in the treatment of affective disorders

Michael J. Owens, Charles B. Nemeroff

Research output: Contribution to journalReview articlepeer-review

20 Scopus citations

Abstract

Since its isolation and characterisation in 1981, corticotropin- releasing factor (CRF) has been found to integrate not only the endocrine, but also the autonomic, immunological and behavioural, responses of mammalian organisms to stress. Direct CNS administration of CRF to laboratory animals produces actions similar to those observed after exposure to stress. Moreover, CNS administration of peptidergic CRF antagonists blocks many of the behavioural responses to stress. Because both early untoward life events as well as recently experienced stress have been implicated in the pathophysiology of affective disorders, and because there is substantial evidence for CRF neuronal hyperactivity in patients with affective disorders, small molecule, lipophilic CRF antagonists have been hypothesised to possess antidepressant activity. Within the last few years, a number of pharmaceutical companies have developed selective, small molecule CRF1 receptor antagonists. These compounds block the effects of CRF both in vitro and in vivo. There is also evidence that these agents possess anxiolytic and antidepressant activity in animal behavioural models. Compounds that act upon the CRF system have been hypothesised to be of value not only for certain psychiatric disorders but also in neurodegenerative and inflammatory disorders. Some of these CRF1 receptor antagonists are currently undergoing clinical trials to determine their efficacy and tolerability in patients with affective disorders.

Original languageEnglish (US)
Pages (from-to)85-92
Number of pages8
JournalCNS Drugs
Volume12
Issue number2
DOIs
StatePublished - Oct 4 1999
Externally publishedYes

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health
  • Pharmacology (medical)

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