Fremanezumab inhibits vasodilatory effects of CGRP and capsaicin in rat cerebral artery - Potential role in conditions of severe vasoconstriction.

08:00 EDT 4th October 2019 | BioPortfolio

Summary of "Fremanezumab inhibits vasodilatory effects of CGRP and capsaicin in rat cerebral artery - Potential role in conditions of severe vasoconstriction."

CGRP plays a major role in the pathophysiology of migraine. Concomitant, CGRP plays a role in endogenous neurovascular protection from severe vasoconstriction associated with e.g. cerebral or cardiac ischemia. The CGRP antagonistic antibodies Fremanezumab (TEVA Pharmaceuticals) and Erenumab (Novartis/Amgen) have successfully been developed for the prevention of frequent migraine attacks. Whereas these antibodies might challenge endogenous neurovasular protection during severe cerebral or coronary vasoconstriction, potential future therapeutic CGRP agonists might induce migraine-like headaches in migraineurs. In the current study segments of cerebral artery have been used to obtain mechanistic insight of the CGRP-neutralizing anti-body Fremanezumab in neurovascular regulation in vitro. The basilar artery was selected due to its relevance in subarachnoid hemorrhage (SAH). Erenumab is known to block the human CGRP receptor and Fremanezumab to neutralize both human and rat CGRP. Results confirmed that Erenumab does not block the rat CGRP receptor and that Fremanezumab inhibits the vasodilatory effect induced by both human CGRP, rat CGRP and the metabolically stable CGRP analog, SAX in rat basilar artery. Fremanezumab also inhibits the vasodilatory effect of capsaicin in constricted segments of basilar artery. Capsaicin is used as a pharmacological tool to induce secretion of endogenous perivascular CGRP and our studies confirm that the antibody reach the perivascular sensory synaptic cleft and blocks the vasodilatory response of released CGRP in the present in vitro model. Thus, CGRP neutralization might have the mechanistic potential to block vasoprotective responses to severe vasoconstriction provided they reach the site of action and Fremanezumab is an important tool for future investigations of the impact of CGRP physiology.


Journal Details

This article was published in the following journal.

Name: European journal of pharmacology
ISSN: 1879-0712
Pages: 172726


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Medical and Biotech [MESH] Definitions

NECROSIS occurring in the ANTERIOR CEREBRAL ARTERY system, including branches such as Heubner's artery. These arteries supply blood to the medial and superior parts of the CEREBRAL HEMISPHERE, Infarction in the anterior cerebral artery usually results in sensory and motor impairment in the lower body.

Pathological conditions of intracranial ARTERIES supplying the CEREBRUM. These diseases often are due to abnormalities or pathological processes in the ANTERIOR CEREBRAL ARTERY; MIDDLE CEREBRAL ARTERY; and POSTERIOR CEREBRAL ARTERY.

Artery formed by the bifurcation of the BASILAR ARTERY. Branches of the posterior cerebral artery supply portions of the OCCIPITAL LOBE; PARIETAL LOBE; inferior temporal gyrus, brainstem, and CHOROID PLEXUS.

A polygonal anastomosis at the base of the brain formed by the internal carotid (CAROTID ARTERY, INTERNAL), proximal parts of the anterior, middle, and posterior cerebral arteries (ANTERIOR CEREBRAL ARTERY; MIDDLE CEREBRAL ARTERY; POSTERIOR CEREBRAL ARTERY), the anterior communicating artery and the posterior communicating arteries.

Artery formed by the bifurcation of the internal carotid artery (CAROTID ARTERY, INTERNAL). Branches of the anterior cerebral artery supply the CAUDATE NUCLEUS; INTERNAL CAPSULE; PUTAMEN; SEPTAL NUCLEI; GYRUS CINGULI; and surfaces of the FRONTAL LOBE and PARIETAL LOBE.

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