CGRP receptor antagonists: A new frontier of anti-migraine medications

Abstract

Migraine is a chronic pain condition that affects 12% of the population. Currently, the most effective treatments are the triptans, but they are limited in their efficacy and have potentially deleterious cardiovascular complications. Based on basic science studies over the past decade, a new generation of anti-migraine drugs is now being developed. At the forefront of these studies is a new calcitonin gene-related peptide (CGRP) receptor antagonist that is as effective as triptans in the acute treatment of migraines, without the cardiovascular effects. This review will address the likely mechanisms and therapeutic potential of CGRP receptor antagonists.

Analgesic Microneedle Patch for Neuropathic Pain Therapy

“…21–23 Although orally available small molecule CGRP antagonists mitigate migraines, they also produced unwanted systemic side effects leading to suspension of clinical trials. 24–26…”

“…There is also a need for improved delivery techniques, particularly for large molecules, such as peptides and proteins to minimize systemic side effects and toxicity. Calcitonin gene-related peptide (CGRP), a neuropeptide synthesized and released by nociceptive sensory neurons, appears to be critical in the development and maintenance of neuropathic pain states (Supporting Information S2). , Nerve or tissue injury caused by trauma or inflammation, for example, triggers the release of CGRP from nociceptive sensory nerve endings and enhances nociceptive neuronal activity by augmenting voltage-gated sodium channels and transient receptor potential cation channel subfamily V member 1, which leads to thermal hyperalgesia and mechanical allodynia. , Selective inhibition of CGRP signaling by systemic blocking of CGRP receptors has demonstrated a promising therapy to treat migraines. − Although orally available small molecule CGRP antagonists mitigate migraines, they also produced unwanted systemic side effects leading to suspension of clinical trials. − …”

Monoclonal antibodies for chronic pain: A practical review of mechanisms and clinical applications

“… 18 Indeed, a lack of major cardiovascular effects is the major advantage of inhibition of CGRP over triptans in terms of tolerability profile. 75 Inhibition of CGRP via mAbs is also less likely to cause other serious adverse events, including liver toxicity observed with some small molecule CGRP receptor antagonists. 76 However, the possible long-term effects of depleting CGRP need to be assessed further in clinical studies.…”