Pharmacological profile of BIBN4096BS, the first selective small molecule CGRP antagonist
Top Cited Papers
- 1 February 2000
- journal article
- Published by Wiley in British Journal of Pharmacology
- Vol. 129 (3) , 420-423
- https://doi.org/10.1038/sj.bjp.0703110
Abstract
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 (Ki) 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.0703110Keywords
This publication has 19 references indexed in Scilit:
- From Micromolar to Nanomolar Affinity: A Systematic Approach To Identify the Binding Site of CGRP at the Human Calcitonin Gene-Related Peptide 1 ReceptorJournal of Medicinal Chemistry, 1998
- Calcitonin gene-related peptide: Vasoactive effects and potential therapeutic roleGeneral Pharmacology: The Vascular System, 1996
- A cDNA Encoding the Calcitonin Gene-related Peptide Type 1 ReceptorJournal of Biological Chemistry, 1996
- The trigeminovascular system and migraine: Studies characterizing cerebrovascular and neuropeptide changes seen in humans and catsAnnals of Neurology, 1993
- Neural Processing of Craniovascular Pain: A Synthesis of the Central Structures Involved in MigraineHeadache: The Journal of Head and Face Pain, 1991
- Vasoactive peptide release in the extracerebral circulation of humans during migraine headacheAnnals of Neurology, 1990
- Release of vasoactive peptides in the extracerebral circulation of humans and the cat during activation of the trigeminovascular systemAnnals of Neurology, 1988
- The neurobiology of vascular head painAnnals of Neurology, 1984
- Alternative RNA processing in calcitonin gene expression generates mRNAs encoding different polypeptide productsNature, 1982
- Relationship between the inhibition constant (KI) and the concentration of inhibitor which causes 50 per cent inhibition (I50) of an enzymatic reactionBiochemical Pharmacology, 1973