Corticotropin releasing hormone antagonist

A Corticotropin releasing hormone antagonist is a specific type of receptor antagonist which blocks the receptor sites for Corticotropin releasing hormone (also known as Corticotropin releasing factor (CRF)), blocking therefore 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 mainly expressed 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

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.