Corticotropin-releasing factor receptor antagonists in affective disorders and drug dependence-- an update.
Dysfunctioning of corticotropin-releasing factor (CRF) and its receptors (CRF(1) and CRF(2)) has been linked to the development of stress-related disorders, such as affective disorders and drug abuse. The molecular characterization of CRF(1) and CRF(2) receptors and their splice variants has generated detailed information on their pharmacology, tissue distribution and physiology. In addition, the recent development of a small molecule CRF(1) antagonist has provided important information on the contribution of this receptor to the development of stress-related diseases. Despite the high homology to the CRF(1) receptor and the generation of peptide-based research tools, the physiological role of the CRF(2) receptor is largely unclear. This is due to different expression patterns in rodents and primates and the lack of brain-penetrant CRF(2)-selective small molecule antagonists. However, the CRF(2) receptor may be important for motivational types of behavior essential for survival, such as feeding and defense and impacts on cardiovascular function.
Steckler
Thomas
T
Johnson & Johnson Pharmaceuticals Research & Development, CNS Drug Discovery, B-2340 Beerse, Belgium. tsteckle@prdbe.jnj.com
Dautzenberg
Frank M
FM
D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism* / Q000503:physiopathology; D008968:Molecular Conformation; D019964:Mood Disorders / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D010455:Peptides / Q000378:metabolism / Q000494:pharmacology; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D013312:Stress, Physiological / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D019966:Substance-Related Disorders / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D000099052:CRF Receptor, Type 1
C101531:CRF receptor type 2; D010455:Peptides; D020033:Protein Isoforms; D018019:Receptors, Corticotropin-Releasing Hormone; D000099052:CRF Receptor, Type 1; D003346:Corticotropin-Releasing Hormone