Migraine and beyond: cardiovascular therapeutic potential for CGRP modulators

Area of Science:

• Cardiovascular Physiology
• Neuroscience
• Pharmacology

Background:

• Calcitonin gene-related peptide (CGRP) is a potent vasodilator involved in neurogenic inflammation, headaches (including migraine), and cardiovascular functions.
• CGRP exhibits cardioprotective effects, acts as a positive inotrope, and increases heart rate, showing therapeutic potential in hypertension, heart failure, and Raynaud's disease.

Purpose of the Study:

• To explore the therapeutic potential of CGRP and its modulators (mimetics and inhibitors) in various physiological and pathological conditions.
• To review the clinical applications and limitations of CGRP-based therapies.

Main Methods:

• Review of existing clinical trials and pharmacological data on CGRP and its analogues.
• Identification of CGRP mimetics (e.g., capsaicin receptor agonists, gene transfer) and inhibitors (e.g., CGRP receptor antagonists, 5-HT1D agonists).

Main Results:

• CGRP's vasodilatory action is beneficial in hypertension, angina, heart failure, and Raynaud's disease, but its short half-life limits clinical use.
• CGRP mimetics, including oral long-acting formulations, may offer new treatment avenues.
• CGRP inhibitors are potential treatments for conditions with excessive CGRP activity, such as migraine and menopausal flushing.

Conclusions:

• CGRP-based therapies, including mimetics and inhibitors, hold significant therapeutic promise for a range of conditions.
• Further development of CGRP mimetics and inhibitors, particularly orally available forms, is warranted to overcome current clinical limitations.