Corticotropin releasing hormone antagonist
Encyclopedia
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.
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
, but so far no highly selective agents for the different CRF-2 subtypes are available.
Receptor antagonist
A receptor antagonist is a type of receptor ligand or drug that does not provoke a biological response itself upon binding to a receptor, but blocks or dampens agonist-mediated responses...
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
Cortisol
Cortisol is a steroid hormone, more specifically a glucocorticoid, produced by the adrenal gland. It is released in response to stress and a low level of blood glucocorticoids. Its primary functions are to increase blood sugar through gluconeogenesis; suppress the immune system; and aid in fat,...
.
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.
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
Antalarmin
Antalarmin is a drug that acts as a CRF-1 antagonist.Corticotropin-releasing factor , also known as Corticotropin-releasing hormone, is an endogenous peptide hormone released in response to various triggers such as chronic stress and drug addiction. This, then, triggers the release of corticotropin...
and a newer drug pexacerfont
Pexacerfont
Pexacerfont is a drug developed by Bristol-Myers Squibb which acts as a CRF-1 antagonist.Corticotropin releasing factor , also known as Corticotropin releasing hormone, is an endogenous peptide hormone which is released in response to various triggers such as chronic stress...
, although several other ligands for this receptor are used in research, such as LWH-234, CP-154,526
CP-154,526
CP-154,526 is a potent and selective antagonist of the corticotropin releasing hormone receptor 1 developed by Pfizer.CP-154,526 is under investigation for the potential treatment of alcoholism.- External links :...
, NBI-27914 and R-121,919. Antagonists acting at CRF-2 have also been developed, such as the peptide Astressin-B
Astressin-B
Astressin-B is a nonselective corticotropin releasing hormone antagonist that reduces the synthesis of ACTH and cortisol.Reducing ACTH synthesis, it improves the sexual drive of rats under stressing conditions....
, but so far no highly selective agents for the different CRF-2 subtypes are available.