Corticotropin-releasing hormone antagonist

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A Corticotropin-releasing hormone antagonist is a specific type of receptor antagonist that blocks the receptor sites for Corticotropin-releasing hormone (also known as Corticotropin-releasing factor (CRF)), thereby blocking the consequent secretions of ACTH and cortisol.

There are four subtypes of this receptor known at present, defined as CRF-1, CRF-2a, CRF-2b, and CRF-2g. Three of these receptors are expressed only in the brain, CRF-1 in the cortex and cerebrum, CRF-2a in the lateral septum and hypothalamus, and CRF-2g in the amygdala. CRF-2b is expressed in the choroid plexus and cerebral arterioles in the brain, but is expressed mainly peripherally on the heart and skeletal muscle tissue.[1]

The main research into CRF antagonists to date has focused on antagonists selective for the CRF-1 subtype. Several antagonists for this receptor have been developed and are widely used in research, with the best-known agents being the selective CRF-1 antagonist antalarmin and a newer drug pexacerfont, although several other ligands for this receptor are used in research, such as LWH-234, CP-154,526, NBI-27914 and R-121,919. Antagonists acting at CRF-2 have also been developed, such as the peptide Astressin-B,[2] but so far no highly selective agents for the different CRF-2 subtypes are available.

References[edit]

  1. ^ McCarthy JR, Heinrichs SC, Grigoriadis DE. Recent advances with the CRF1 receptor: design of small molecule inhibitors, receptor subtypes and clinical indications. Current Pharmaceutical Design. 1999 May; 5(5):289-315.
  2. ^ Vulliemoz NR, Xiao E, Xia-Zhang L, Rivier J, Ferin M. Astressin B, a non selective CRH receptor antagonist, prevents the inhibitory effect of Ghrelin on LH pulse frequency in the ovariectomized rhesus monkey. Endocrinology. 2007 Dec 6.