Calcitonin gene-related peptide

Summary

Calcitonin gene-related peptide (CGRP) is an endogenous neuropeptide produced by alternative splicing of the calcitonin gene, existing in alpha and beta isoforms. It is a key mediator of migraine pathophysiology and cardiovascular regulation. As an exogenous therapeutic agent, CGRP itself is primarily used in research; however, it has served as the foundational target for a class of approved anti-migraine therapies including CGRP receptor antagonists (gepants) and anti-CGRP/anti-CGRP receptor monoclonal antibodies (erenumab, fremanezumab, galcanezumab, eptinezumab).

Mechanism of Action

Endogenous 37-amino acid neuropeptide that acts as a potent vasodilator by binding to CGRP receptors (CLR/RAMP1 heterodimer), activating adenylyl cyclase and increasing cAMP, leading to smooth muscle relaxation; also modulates nociceptive signaling in trigeminal neurons and plays roles in neurogenic inflammation

Routes of Administration

Goals & Uses

• Pain modulation researchResearchModerate
• Wound healing / tissue protectionResearchLow
• Migraine research / provocation modelResearchHigh
• Cardiovascular vasodilation researchResearchModerate

Contraindications

• Severe cardiovascular diseaseCardiovascularHigh
• Active myocardial ischemiaCardiovascularHigh
• Known hypersensitivity to CGRPAllergic/ImmunologicHigh

Adverse Effects

• Injection site reactionsLocalUncommon
• HypotensionCardiovascularUncommonLow blood pressure
• FlushingVascularCommonWarmth and redness of the skin
• Headache / migraineNeurologicalCommon
• Reflex tachycardiaCardiovascularUncommon

Drug Interactions

• NitratesModerate
• Antihypertensive agentsModerate
• Vasoconstrictors (e.g., triptans, ergotamines)Moderate

Population Constraints

• PregnancyReproductive SafetyRelative
• Elderly patients with cardiovascular diseaseCardiovascularRelative
• Pediatric patientsAgeRelative
• Patients with uncontrolled hypertensionCardiovascularRelative

Regulatory Status

• European UnionUnapprovedNot approved as a therapeutic agent by EMA. Used in clinical research settings for migraine provocation studies.
• United StatesUnapprovedCGRP itself is not an approved therapeutic. Anti-CGRP monoclonal antibodies and gepants are FDA-approved for migraine. CGRP is used in IND-covered research protocols.
• United KingdomUnapprovedNot approved by MHRA as a therapeutic. Used experimentally in academic and clinical research.

CGRP as an exogenous peptide is not itself an approved therapeutic agent. It is used experimentally to provoke migraine attacks in research settings. Anti-CGRP therapies targeting this peptide or its receptor are FDA/EMA approved for migraine prevention and acute treatment.

Evidence & Sources

No sources recorded yet.