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      Characterizing the PK/PD relationship for inhibition of capsaicin-induced dermal vasodilatation by MK-3207, an oral calcitonin gene related peptide receptor antagonist.

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          Abstract

          Calcitonin gene related peptide (CGRP) receptor antagonists are effective acute migraine treatments. A capsaicin-induced dermal vasodilatation (CIDV) model has been developed to provide target-engagement information in healthy volunteers. In the model, CGRP release is provoked after dermal capsaicin application, by activating transient receptor potential vanilloid-type-1 (TRPV1) receptors at peripheral sensory nerves. Laser Doppler imaging is used to quantify CIDV and subsequent inhibition by CGRP receptor antagonists. We sought to evaluate a CGRP receptor antagonist, MK-3207, in the biomarker model and to assess the predictability of the CIDV response to migraine clinical efficacy.

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          Author and article information

          Journal
          Br J Clin Pharmacol
          British journal of clinical pharmacology
          Wiley-Blackwell
          1365-2125
          0306-5251
          May 2015
          : 79
          : 5
          Affiliations
          [1 ] Merck Research Laboratories, Merck & Co., Inc., Whitehouse Station, NJ, USA.
          Article
          10.1111/bcp.12547
          4415719
          25377933
          f67a4f44-6c42-4628-bf28-f0ae1e98d73f

          CGRP, MK-3207, capsaicin, human, vasodilatation

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