CRF Receptor Antagonists: Utility in Research and Clinical Practice

Chatzaki, E.; Minas, V.; Zoumakis, E.; Makrigiannakis, A.
September 2006
Current Medicinal Chemistry;2006, Vol. 13 Issue 23, p2751
Academic Journal
CRF, CRF-related peptides and CRF receptors constitute a complex physiological system which has a key role in facilitating the adaptation of the organism to the stressful stimuli of the environment. The behavioral, endocrine, autonomic and immune branches of stress response are considered to be under the coordinating effects of CRF and its related peptides. The effects of these peptides are mediated through two distinct receptors, types 1 and 2 CRF receptors (CRF1 and CRF2). The two receptors are encoded by separate genes and belong to the G-coupled receptor superfamily. The wide influence of the CRF system on physiological processes in both brain and periphery, suggests the implication of the respective peptides in the pathophysiology of numerous disorders which involve dysregulated stress responses. The potential use of CRF antagonists in such disorders is currently under intense investigation. Furthermore, such compounds have been invaluable in elucidating the physiology of the CRF system. This review will focus on existing data on the structural and pharmacological characteristics as well as the experimental and potential clinical uses of non-peptide, small molecule CRF antagonists.


Related Articles

  • Expression of Corticotropin-Releasing Hormone Type 1 Receptor in Paraventricular Nucleus after Acute Stress. Imaki, Toshihiro; Katsumata, Harumi; Miyata, Mariko; Naruse, Mitsuhide; Imaki, Junko; Minami, Shiro // Neuroendocrinology;2001, Vol. 73 Issue 5, p293 

    We have previously proposed the existence of ultrashort loop-positive feedback regulation of corticotropin-releasing hormone (CRH) in the hypothalamus. To gain a better understanding of this effect, we performed double-label in situ hybridization to identify the neurons in the paraventricular...

  • The Brave and the Spineless. Keller, Julia C. // Science & Spirit;Sep/Oct2005, Vol. 16 Issue 5, p22 

    Reports on the finding that the way a busy bee responds to stress is similar to what humans do when under duress. Research by scientists from the Netherlands on the DNA of both honeybees and carp; Similarities in a gene sequence for a protein that binds a corticotrophin-releasing stress hormone;...

  • Corticotropin-Releasing Factor Receptor Antagonists in Affective Disorders and Drug Dependence - An Update. Steckler, Thomas; Dautzenberg, Frank M. // CNS & Neurological Disorders - Drug Targets;2006, Vol. 5 Issue 2, p147 

    Dysfunctioning of corticotropin-releasing factor (CRF) and its receptors (CRF1 and CRF2) has been linked to the development of stress-related disorders, such as affective disorders and drug abuse. The molecular characterization of CRF1 and CRF2 receptors and their splice variants has generated...

  • The Role of Corticotropin-Releasing Hormone in the Pathophysiology of Depression: Therapeutic Implications. Lloyd, R. Brett; Nemeroff, Charles B. // Current Topics in Medicinal Chemistry;Mar2011, Vol. 11 Issue 6, p609 

    Stress responses have been posited to be a key component of mental health and disease by playing essential roles both in normal adaptive processes and maladaptive physiological responses that in part underlie the pathogenesis of certain subtypes of mood and anxiety disorders. Early research...

  • Identification of molecules potentially involved in mediating the in vivo actions of the corticotropin-releasing hormone receptor 1 antagonist, NBI30775 (R121919). Post, Anke; Ohl, Frauke; Almeida, Osborne F. X.; Binder, Elisabeth B.; Rücker, Monika; Welt, Sandra; Binder, Elke; Holsboer, Florian; Sillaber, Inge // Psychopharmacology;Jun2005, Vol. 180 Issue 1, p150 

    Presents a study which discussed the molecules potentially involved in mediating the in vivo actions of the corticotropin-releasing hormone (CRH) receptor 1 antagonist NBI30775. Role of the neuropeptide CRH; Link between the hyperactivity of the hypothalamic-pituitary-adrenal axis with mood and...

  • Association of a corticotropin-releasing hormone receptor 1 haplotype and antidepressant treatment response in Mexican-Americans. Licinio, J.; O'Kirwan, F.; Irizarry, K.; Merriman, B.; Thakur, S.; Jepson, R.; Lake, S.; Tantisira, K. G.; Weiss, S. T.; Wong, M.-L. // Molecular Psychiatry;Dec2004, Vol. 9 Issue 12, p1075 

    There are well-replicated, independent lines of evidence supporting a role for corticotropin-releasing hormone (CRH) in the pathophysiology of depression. CRH receptor 1 (CRHR1), which we first mapped in the brain in 1994, has been implicated in the treatment of depression and anxiety. We...

  • Behavioural genetics: Dipsomaniac mice? López, Juan Carlos // Nature Reviews Genetics;Jun2002, Vol. 3 Issue 6, p408 

    Discusses research on the enhanced and delayed stress-induced alcohol drinking in mice lacking functional corticotropin-releasing hormone (CRH). Reference to a study by L. Sillaber and colleagues published in the 2002 issue of "Science" journal; Influence of stress on alcohol intake; CRH...

  • The CRF Receptor Structure, Function and Potential for Therapeutic Intervention. Grigoriadis, D.E.; Haddach, M.; Ling, N.; Saunders, J. // Current Medicinal Chemistry - Central Nervous System Agents;May2001, Vol. 1 Issue 1, p63 

    Two distinct sub-types of receptor encoded by separate genes have been described to date, CRF1 and CRF2, and they belong to the Class-B subdivision within the G-protein coupled receptor (GPCR) super family. All known CRF receptors positively regulate the accumulation of cAMP in response to CRF...

  • Corticotropin-Releasing Factor Binding Protein - A Ligand Trap? Jahn, Olaf; Radulovic, Jelena; Stiedl, Oliver; Tezval, Hossein; Eckart, Klaus; Spiess, Joachim // Mini Reviews in Medicinal Chemistry;Oct2005, Vol. 5 Issue 10, p953 

    The actions of the neuropeptide corticotropin-releasing factor (CRF) are modulated by a CRF binding protein (CRFBP). In view of the memory-enhancing effects of CRF, the release of endogenous CRF from CRFBP by CRFBP inhibitors has been suggested as a therapeutical strategy for the treatment of...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics