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Can CRF 1 receptor antagonists become antidepressant and/or anxiolytic agents?
Author(s) -
Overstreet David H.,
Knapp Darin J.,
Breese George R.
Publication year - 2005
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.20023
Subject(s) - anxiolytic , anxiogenic , antidepressant , anxiety , psychology , pharmacology , receptor , elevated plus maze , medicine , psychiatry
Significant progress has been made in the development of several nonpeptide antagonists of the type 1 receptor for corticotropin‐releasing factor (CRF). The present review outlines the properties of this drug class that point to their potential as agents for depression and/or anxiety. Behavioral tests of CRF 1 receptor antagonists relevant to depression have been mixed. For example, most CRF 1 receptor antagonists did not lower swim test immobility in a subacute paradigm, where three injections of the drug are given in the 24 hrs between a 15‐min pre‐swim and a 5‐min test swim. However, reliable effects in other tests of antidepressant action were observed in the chronic mild stress protocol or the Flinders Sensitive Line rat that exhibits innately high swim test immobility when the drugs were given chronically. Because these latter tests have a very good record of predicting antidepressant activity, CRF 1 receptor antagonists are good candidates for clinical trials for depression. Evidence indicates that the CRF 1 receptor antagonists do not exhibit changes in anxiety‐like behavior under basal conditions. However, this drug class effectively blocks the anxiogenic states produced by withdrawal from chronic alcohol, by exposure to stress, or in rats selectively bred for high anxiety. CRF 1 receptor antagonists also prevent the anxiety associated with multiple ethanol withdrawals when given only during the earlier withdrawals. Thus, these agents may also have clinically relevant anxiolytic effects, not only in individuals with anxiety disorders but also in individuals who have anxiety episodes during alcohol or drug withdrawal. Drug Dev. Res. 65:191–204, 2005. © 2005 Wiley‐Liss, Inc.