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Pharmacological profile of BIBN4096BS, the first selective small molecule CGRP antagonist
Author(s) -
Doods Henri,
Hallermayer Gerhard,
Wu Dongmei,
Entzeroth Michael,
Rudolf Klaus,
Engel Wolfhard,
Eberlein Wolfgang
Publication year - 2000
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0703110
Subject(s) - calcitonin gene related peptide , marmoset , antagonist , trigeminal ganglion , pharmacology , migraine , receptor , in vivo , stimulation , chemistry , medicine , neuroscience , endocrinology , neuropeptide , biology , paleontology , microbiology and biotechnology , sensory system
Calcitonin gene‐related peptide (CGRP) is one of the most potent endogenous vasodilators known. This peptide is increased during migraine attacks and has been implicated in the pathogenesis of migraine headache. Here we report on the first small molecule selective CGRP antagonist: BIBN4096BS. In vitro , this compound is extremely potent at primate CGRP receptors exhibiting an affinity ( K i ) for human CGRP receptors of 14.4±6.3 ( n =4) pM. In an in vivo model, BIBN4096BS in doses between 1 and 30 μg kg −1 (i.v.) inhibited the effects of CGRP, released by stimulation of the trigeminal ganglion, on facial blood flow in marmoset monkeys. It is concluded that BIBN4096BS is a potent and selective CGRP antagonist. British Journal of Pharmacology (2000) 129 , 420–423; doi: 10.1038/sj.bjp.0703110