Corticotropin-releasing factor/hormone receptor

Pseudohypericin has been shown to be a corticotropin-releasing factor (CRF), receptor antagonist. CRF has been implicated as a pathogenic factor in affective disorders, with elevated levels that are normalized after treatment with antidepressants found in the cerebrospinal fluid of patients with depression. CRF acts on CRFX receptors in the pituitary gland to stimulate the release of adrenocoticotropic hormone, which stimulates the release of glucocorticoid stress hormones from the adrenal glands (19). It is possible that St. John s wort s activity comes from pseudohypericin s ability to block the CRFX receptor. 

Bale TL, Contarino A, Smith GW, Chan R, Gold LH, Sawchenko PE, Koob GF, Vale WW, Lee KF (2000) Mice deficient for corticotropin-releasing hormone receptor-2 display anxiety-like behaviour and are hypersensitive to stress. Nat Genet 24 410-414 Bale TL, Picetti R, Contarino A, Koob GF, Vale WW, Lee KF (2002) Mice deficient for both corticotropin-releasing factor receptor 1 (CRFRl) and CRFR2 have an impaired stress response and display dichotomous anxiety-like behavior. J Neurosci 22 193-199 Barberis C, Tribollet M (1996) Vasopressin and oxytocin receptors in the central nervous system. Grit RevNeurobiol 10 119-154... 

Cao, J., Papadopoulou, N., Kempuraj, D., Boucher, W.S., Sugimoto, K., Cetrulo, C.L., and Theoharides, T.C. 2005. Human mast cells express corticotropin-releasing hormone (CRH) receptors and CRH leads to selective secretion of vascular endothelial growth factor. J Immunol 174 7665-7675. 

Based on a new substantial body of pharmacological and clinical evidence, it is anticipated that the modulation of the effects of corticotropin releasing hormone or factor (CRH or CRF) may eventually play a role in the treatment of depression or anxiety-related disorders. This interest in CRH as a new important target for drug discovery is clearly evident. Recently Gilligan et al. [74] have observed that the Suzuki reaction can be used to synthesize a variety of aryl-substituted heterocyclic antagonists of the CRH receptor (Eq. (43)). 

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