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Calcitonin Gene-Related Peptide Antagonists and Therapeutic Antibodies

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Calcitonin Gene-Related Peptide (CGRP) Mechanisms

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 255))

Abstract

The calcitonin gene-related peptide (CGRP) receptor is composed of the calcitonin receptor-like receptor (CLR, a class B GPCR) and a single-pass membrane protein known as receptor activity modifying protein type 1 (RAMP1). The levels of the CGRP peptide increase during a migraine attack and infusion of CGRP can provoke a migraine attack. Consequently, there is much interest in inhibiting the actions of CGRP as a way to control migraine. Here we describe the development of small molecule antagonists designed to bind to the CGRP receptor to block its action by preventing binding of the CGRP peptide. We also describe the development of antibody drugs, designed to bind either to the CGRP receptor to block its action, or to bind directly to the CGRP peptide. The field has been very active, with one antibody drug approved and three antibody drugs in phase III clinical trial. Initial programs on the development CGRP antagonists were frustrated by liver toxicity but the current outlook is very promising with five small molecule antagonists in various stages of clinical trial.

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Authors and Affiliations

  1. School of Biological Sciences, University of Essex, Colchester, UK

    Roxana-Maria Rujan & Christopher A. Reynolds

Authors
  1. Roxana-Maria Rujan
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  2. Christopher A. Reynolds
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Correspondence to Christopher A. Reynolds .

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Editors and Affiliations

  1. School of Cardiovascular Medicine & Sciences, King’s College London, London, UK

    Susan D. Brain

  2. Department of Health Sciences, University of Florence, Florence, Italy

    Pierangelo Geppetti

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Rujan, RM., Reynolds, C.A. (2018). Calcitonin Gene-Related Peptide Antagonists and Therapeutic Antibodies. In: Brain, S., Geppetti, P. (eds) Calcitonin Gene-Related Peptide (CGRP) Mechanisms. Handbook of Experimental Pharmacology, vol 255. Springer, Cham. https://doi.org/10.1007/164_2018_173

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