Melanocortin receptors are members of the rhodopsin

Rhodopsin

Rhodopsin, also known as visual purple, is a biological pigment of the retina that is responsible for both the formation of the photoreceptor cells and the first events in the perception of light. Rhodopsins belong to the G-protein coupled receptor family and are extremely sensitive to light,...

 family of 7-transmembrane, G protein-coupled receptors.

There are five known members of the melanocortin receptor system each with differing specificities for melanocortin

Melanocortin

The melanocortins are a group of peptide hormones which include adrenocorticotropic hormone and the different forms of melanocyte-stimulating hormone . They can be synthetic . In humans they can be endogenously produced from proopiomelanocortin in the pituitary gland...

s:
. MC1R is associated with pigmentation genetics.. MC2R is also known as the ACTH receptor

ACTH receptor

The ACTH receptor is a type of melanocortin receptor , properly known as MC2, which is specific for ACTH.It is found in the zona fasciculata of the human adrenal cortex. Binding of the receptor by ACTH stimulates the production of cortisol...

 or corticotropin receptor because it is specific for ACTH alone.. MC3R. Defects in MC4R are a cause of autosomal dominant obesity

Obesity

Obesity is a medical condition in which excess body fat has accumulated to the extent that it may have an adverse effect on health, leading to reduced life expectancy and/or increased health problems...

, accounting for 6% of all cases of early-onset obesity.. MC5R
These receptors are inhibited

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...

 by endogenous

Endogenous

Endogenous substances are those that originate from within an organism, tissue, or cell. Endogenous retroviruses are caused by ancient infections of germ cells in humans, mammals and other vertebrates...

 inverse agonist

Inverse agonist

In the field of pharmacology, an inverse agonist is an agent that binds to the same receptor as an agonist but induces a pharmacological response opposite to that agonist....

s agouti signalling peptide

Agouti signalling peptide

Agouti signalling peptide, a product of the Agouti gene, is a peptide consisting of 131 amino acids. Its discovery was published in 1994 in the scientific journal Nature where its functional properties were described...

 and agouti-related peptide

Agouti-related peptide

Agouti-related protein also called Agouti-related peptide is a neuropeptide produced in the brain by the AgRP/NPY neuron. It is only synthesised in NPY containing cell bodies located in the ventromedial part of the arcuate nucleus in the hypothalamus...

, and activated by synthetic

Peptide synthesis

In organic chemistry, peptide synthesis is the production of peptides, which are organic compounds in which multiple amino acids are linked via amide bonds which are also known as peptide bonds...

 (i.e.: afamelanotide

Afamelanotide

Afamelanotide developed at the University of Arizona is a synthetic analog of the naturally-occurring melanocortin peptide hormone alpha-melanocyte stimulating hormone that has been shown to induce skin pigmentation through melanogenesis and thereby subsequently reduce sun damage to UV exposed...

) and endogenous agonist

Agonist

An agonist is a chemical that binds to a receptor of a cell and triggers a response by that cell. Agonists often mimic the action of a naturally occurring substance...

 melanocyte-stimulating hormone

Melanocyte-stimulating hormone

The melanocyte-stimulating hormones are a class of peptide hormones that are produced by cells in the intermediate lobe of the pituitary gland...

s.

Selective Ligands

Several selective ligand

Ligand

In coordination chemistry, a ligand is an ion or molecule that binds to a central metal atom to form a coordination complex. The bonding between metal and ligand generally involves formal donation of one or more of the ligand's electron pairs. The nature of metal-ligand bonding can range from...

s for the melanocortin receptors are known, and some synthetic compounds have been investigated as potential tanning, anti-obesity and aphrodisiac drugs, with tanning effects mainly from stimulation of MC₁, while anorectic and aphrodisiac effects appear to involve both MC₃ and MC₄. MC₁, MC₃ and MC₄ are widely expressed in the brain, and are also thought to be responsible for effects on mood and cognition.

Agonists

Non-selective

• Afamelanotide
  Afamelanotide
  Afamelanotide developed at the University of Arizona is a synthetic analog of the naturally-occurring melanocortin peptide hormone alpha-melanocyte stimulating hormone that has been shown to induce skin pigmentation through melanogenesis and thereby subsequently reduce sun damage to UV exposed...
  
  
• alpha-MSH
• Bremelanotide
  Bremelanotide
  Bremelanotide is a compound under drug development by Palatin Technologies as a treatment for hemorrhagic shock and reperfusion injury...
  
  
• Melanotan II
  Melanotan II
  Melanotan II developed at the University of Arizona is a synthetic analog of the naturally occurring melanocortin peptide hormone alpha-melanocyte stimulating hormone that in usage has been shown to have melanogenesis and aphrodisiac effects in preliminary studies and clinical trials...
  
  

MC₂ selective

• ACTH
  Adrenocorticotropic hormone
  Adrenocorticotropic hormone , also known as 'corticotropin', 'Adrenocorticotrophic hormone', is a polypeptide tropic hormone produced and secreted by the anterior pituitary gland. It is an important component of the hypothalamic-pituitary-adrenal axis and is often produced in response to biological...
  
  
• Cosyntropin
  Cosyntropin
  Cosyntropin is a synthetic derivative of adrenocorticotropic hormone that is used in the ACTH stimulation test to evaluate and diagnose cortisol disorders...
  
  
• Tetracosactide
  Tetracosactide
  Tetracosactide is a synthetic analogue of the naturally occurring adrenocorticotrophic hormone .-Pharmacology:...
  
  

MC₃ selective

• gamma-MSH

MC₄ selective

• beta-MSH
• THIQ
  THIQ
  THIQ is a drug used in scientific research, which is the first non-peptide agonist developed that is selective for the melanocortin receptor subtype MC4. In animal studies, THIQ stimulated sexual activity in rats, but with little effect on appetite or inflammation...
  
  

Antagonists and inverse agonists

MC₁ selective

• Agouti signalling peptide
  Agouti signalling peptide
  Agouti signalling peptide, a product of the Agouti gene, is a peptide consisting of 131 amino acids. Its discovery was published in 1994 in the scientific journal Nature where its functional properties were described...
  
  

MC₄ selective

• Agouti-related peptide
  Agouti-related peptide
  Agouti-related protein also called Agouti-related peptide is a neuropeptide produced in the brain by the AgRP/NPY neuron. It is only synthesised in NPY containing cell bodies located in the ventromedial part of the arcuate nucleus in the hypothalamus...
  
  (inverse agonist at both MC₃ and MC₄)
• HS-014
• HS-024
• MCL-0042
• MCL-0129
• MPB-10
• SHU-9119 (agonist at MC₁ and MC₅, antagonist at MC₃ and MC₄)

External links

• Calculated spatial position of melanocortin-4 receptor in the lipid bilayer, inactive state with antagonist and active state with agonist