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 micrograms 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.
MeSH terms
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Animals
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Blood Pressure / drug effects
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Calcitonin Gene-Related Peptide / antagonists & inhibitors*
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Callithrix
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Cell Line
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Cyclic AMP / biosynthesis
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Electric Stimulation
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Face / blood supply
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Female
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Humans
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Kinetics
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Male
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Migraine Disorders / drug therapy
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Piperazines / pharmacology*
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Piperazines / therapeutic use
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Quinazolines / pharmacology*
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Quinazolines / therapeutic use
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Rats
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Receptors, Calcitonin Gene-Related Peptide / drug effects
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Receptors, Calcitonin Gene-Related Peptide / metabolism
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Regional Blood Flow / drug effects
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Trigeminal Ganglion / drug effects
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Trigeminal Ganglion / physiology
Substances
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Piperazines
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Quinazolines
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Receptors, Calcitonin Gene-Related Peptide
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Cyclic AMP
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Calcitonin Gene-Related Peptide
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olcegepant