Pharmacological profile of BIBN4096BS, the first selective small molecule CGRP antagonist.
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.
Doods
H
H
Boehringer Ingelheim Pharma KG, Biberach, Germany. henri.doods@bc.boehringer-ingelheim.com
Hallermayer
G
G
Wu
D
D
Entzeroth
M
M
Rudolf
K
K
Engel
W
W
Eberlein
W
W
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D015740:Calcitonin Gene-Related Peptide / Q000037:antagonists & inhibitors*; D002144:Callithrix; D002460:Cell Line; D000242:Cyclic AMP / Q000096:biosynthesis; D004558:Electric Stimulation; D005145:Face / Q000098:blood supply; D005260:Female; D006801:Humans; D007700:Kinetics; D008297:Male; D008881:Migraine Disorders / Q000188:drug therapy; D010879:Piperazines / Q000494:pharmacology* / Q000627:therapeutic use; D011799:Quinazolines / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000187:drug effects / Q000378:metabolism; D012039:Regional Blood Flow / Q000187:drug effects; D012668:Trigeminal Ganglion / Q000187:drug effects / Q000502:physiology
D010879:Piperazines; D011799:Quinazolines; D018015:Receptors, Calcitonin Gene-Related Peptide; D000242:Cyclic AMP; D015740:Calcitonin Gene-Related Peptide; C406305:olcegepant