Calcitonin gene-related peptide (CGRP) receptor antagonists are a class of drugs that act as

antagonist An antagonist is a character in a story who is presented as the chief foe of the protagonist. Etymology The English word antagonist comes from the Greek ἀνταγωνιστής – ''antagonistēs'', "opponent, competitor, villain, enemy, riv ...

s of the

calcitonin gene-related peptide receptor Calcitonin receptor-like (CALCRL), also known as the calcitonin receptor-like receptor (CRLR), is a human protein; it is a receptor for calcitonin gene-related peptide. Function The protein encoded by the CALCRL gene is a G protein-coupled rec ...

(CGRPR). Several

monoclonal antibodies A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a cell Lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell. Monoclonal antibodies ca ...

which binds to the CGRP receptor or peptide have been approved for prevention of migraine. Three

small molecule Within the fields of molecular biology and pharmacology, a small molecule or micromolecule is a low molecular weight (≤ 1000 daltons) organic compound that may regulate a biological process, with a size on the order of 1 nm. Many drugs ar ...

CGRPR antagonists are approved in the U.S. as

antimigraine agent Antimigraine drugs are medications intended to reduce the effects or intensity of migraine headache. They include drugs for the treatment of acute migraine symptoms as well as drugs for the prevention of migraine attacks. Treatment of acute symp ...

s. Drugs of this class have also been investigated for use in

osteoarthritis Osteoarthritis (OA) is a type of degenerative joint disease that results from breakdown of joint cartilage and underlying bone which affects 1 in 7 adults in the United States. It is believed to be the fourth leading cause of disability in the w ...

Examples

Non-peptide small molecules

Ubrogepant Ubrogepant, sold under the brand name Ubrelvy, is a medication used for the acute (immediate) treatment of migraine with or without aura (a sensory phenomenon or visual disturbance) in adults. It is not indicated for the preventive treatment of ...

is approved for acute treatment of migraines *

Rimegepant Rimegepant, sold under the brand name Nurtec ODT among others, is a medication used for the acute treatment of migraine with or without aura (migraine), aura in adults and the preventative treatment of episodic migraine in adults. It is taken O ...

(BMS-927711) is approved for acute and preventative treatment of migraines * Atogepant (AGN-241689) is approved for preventative treatment of migraines *

Telcagepant Telcagepant (INN) (code name MK-0974) is a calcitonin gene-related peptide receptor antagonist which was an investigational drug for the acute treatment and prevention of migraine, developed by Merck & Co. In the acute treatment of migraine, ...

(MK-0974), reached phase III clinical trials; development discontinued in 2011. *

Olcegepant Olcegepant (INN Inns are generally establishments or buildings where travelers can seek lodging, and usually, food and drink. Inns are typically located in the country or along a highway; before the advent of motorized transportation they also ...

(BIBN-4096BS) is a drug candidate * BI 44370 TA (BI 44370) * MK-3207 * SB-268262

Monoclonal antibodies targeting the CGRP receptor

Erenumab Erenumab, sold under the brand name Aimovig, is a medication which targets the calcitonin gene-related peptide receptor (CGRPR) for the prevention of migraine. It is administered by subcutaneous injection. Erenumab, which was developed by Amg ...

(AMG-334) is approved for prevention of migraine.

Monoclonal antibodies targeting the CGRP molecule

Eptinezumab Eptinezumab, sold under the brand name Vyepti, is a medication used for the preventive treatment of migraine in adults. It is a monoclonal antibody that targets calcitonin gene-related peptides (CGRP) alpha and beta. It is administered by intrav ...

(ALD403) is approved for prevention of migraine. *

Fremanezumab Fremanezumab, sold under the brand name Ajovy, is a medication used to prevent migraines in adults. It is given by injection under the skin. The most common side effect is pain and redness at the site of injection. Other side effects include ...

(TEV-48125) is approved for prevention of migraine. *

Galcanezumab Galcanezumab, sold under the brand name Emgality, is a humanized monoclonal antibody used for the prevention of migraine. It is also used for cluster headaches. Common side effects include pain or redness at the site of injection. Other side ...

(LY2951742) is approved for prevention of migraine and

cluster headache Cluster headache (CH) is a neurological disorder characterized by recurrent severe headaches on one side of the head, typically around the eye(s). There is often accompanying eye watering, nasal congestion, or swelling around the eye on the a ...

Necrotizing fasciitis

A study has found

botox Botulinum toxin, or botulinum neurotoxin (BoNT), is a neurotoxic protein produced by the bacterium ''Clostridium botulinum'' and related species. It prevents the release of the neurotransmitter acetylcholine from axon endings at the neurom ...

effective against

necrotizing fasciitis Necrotizing fasciitis (NF), also known as flesh-eating disease, is a bacterial infection that results in the death of parts of the body's soft tissue. It is a severe disease of sudden onset that spreads rapidly. Symptoms usually include red or p ...

caused by ''

S. pyogenes ''Streptococcus pyogenes'' is a species of Gram-positive, aerotolerant bacteria in the genus ''Streptococcus''. These bacteria are extracellular, and made up of non-motile and non-sporing cocci (round cells) that tend to link in chains. They are ...

'' in mice. Its mechanism of action is by blocking CGRP receptor of nerve cells, which trigger intense pain and activate CGRP cascade, which prevents the immune system attacks to control the pathogen. Botox blocks the CGRP cascade of nerve cells.

Migraine

As of 2018,

erenumab Erenumab, sold under the brand name Aimovig, is a medication which targets the calcitonin gene-related peptide receptor (CGRPR) for the prevention of migraine. It is administered by subcutaneous injection. Erenumab, which was developed by Amg ...

, trade name Aimovig, was approved in the U.S. for use for migraines. It interacts by blocking the CGRP receptor. As of 2018,

fremanezumab Fremanezumab, sold under the brand name Ajovy, is a medication used to prevent migraines in adults. It is given by injection under the skin. The most common side effect is pain and redness at the site of injection. Other side effects include ...

, trade name Ajovy, was approved in the U.S. for use for migraines. It interacts with the CGRP protein expressed during an attack. The third approved treatment, as of 2018,

galcanezumab Galcanezumab, sold under the brand name Emgality, is a humanized monoclonal antibody used for the prevention of migraine. It is also used for cluster headaches. Common side effects include pain or redness at the site of injection. Other side ...

, trade name Emgality, was approved in the U.S. for use in migraines. It also interacts with the protein. As of February 2020, Vyepti (

eptinezumab Eptinezumab, sold under the brand name Vyepti, is a medication used for the preventive treatment of migraine in adults. It is a monoclonal antibody that targets calcitonin gene-related peptides (CGRP) alpha and beta. It is administered by intrav ...

) was FDA approved for the treatment of migraine via intravenous infusion as well. Three small-molecule antagonists have been approved for treatment of migraine: ubrogepant, rimegepant, and atogepant. Ubrogepant and rimegepant are approved for acute treatment. Atogepant and rimegepant are approved for preventative treatment.

Metabolic health

Mice given a CGRP receptor antagonist improved insulin secretion and reduced chronic inflammation, improving the metabolic health of the animals.

References

Antimigraine drugs Receptor antagonists {{nervous-system-drug-stub