Literature DB >> 10711339

Pharmacological profile of BIBN4096BS, the first selective small molecule CGRP antagonist.

H Doods1, G Hallermayer, D Wu, M Entzeroth, K Rudolf, W Engel, W Eberlein.   

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.

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Year:  2000        PMID： 10711339      PMCID： PMC1571877          DOI： 10.1038/sj.bjp.0703110

Source DB:  PubMed          Journal:  Br J Pharmacol        ISSN： 0007-1188            Impact factor:   8.739


  16 in total

1.  Neural processing of craniovascular pain: a synthesis of the central structures involved in migraine.

Authors:  P J Goadsby; A S Zagami; G A Lambert
Journal:  Headache       Date:  1991-06       Impact factor: 5.887

2.  pAx and competitive drug antagonism.

Authors:  H O SCHILD
Journal:  Br J Pharmacol Chemother       Date:  1949-09

Review 3.  Central nervous system binding sites for calcitonin and calcitonin gene-related peptide.

Authors:  P M Sexton
Journal:  Mol Neurobiol       Date:  1991       Impact factor: 5.590

4.  Relationship between the inhibition constant (K1) and the concentration of inhibitor which causes 50 per cent inhibition (I50) of an enzymatic reaction.

Authors:  Y Cheng; W H Prusoff
Journal:  Biochem Pharmacol       Date:  1973-12-01       Impact factor: 5.858

5.  Vasoactive peptide release in the extracerebral circulation of humans during migraine headache.

Authors:  P J Goadsby; L Edvinsson; R Ekman
Journal:  Ann Neurol       Date:  1990-08       Impact factor: 10.422

6.  Calcitonin gene-related peptide receptor antagonist human CGRP-(8-37).

Authors:  T Chiba; A Yamaguchi; T Yamatani; A Nakamura; T Morishita; T Inui; M Fukase; T Noda; T Fujita
Journal:  Am J Physiol       Date:  1989-02

Review 7.  Neurovascular and molecular mechanisms in migraine headaches.

Authors:  M A Moskowitz; R Macfarlane
Journal:  Cerebrovasc Brain Metab Rev       Date:  1993

8.  The trigeminovascular system and migraine: studies characterizing cerebrovascular and neuropeptide changes seen in humans and cats.

Authors:  P J Goadsby; L Edvinsson
Journal:  Ann Neurol       Date:  1993-01       Impact factor: 10.422

9.  Release of vasoactive peptides in the extracerebral circulation of humans and the cat during activation of the trigeminovascular system.

Authors:  P J Goadsby; L Edvinsson; R Ekman
Journal:  Ann Neurol       Date:  1988-02       Impact factor: 10.422

10.  The neurobiology of vascular head pain.

Authors:  M A Moskowitz
Journal:  Ann Neurol       Date:  1984-08       Impact factor: 10.422
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  109 in total

1.  Pharmacological evidence for CGRP uptake into perivascular capsaicin sensitive nerve terminals.

Authors:  A Sams-Nielsen; C Orskov; I Jansen-Olesen
Journal:  Br J Pharmacol       Date:  2001-03       Impact factor: 8.739

2.  Blockade and reversal of spinal morphine tolerance by peptide and non-peptide calcitonin gene-related peptide receptor antagonists.

Authors:  K J Powell; W Ma; M Sutak; H Doods; R Quirion; K Jhamandas
Journal:  Br J Pharmacol       Date:  2000-11       Impact factor: 8.739

3.  BIBN4096BS is a potent competitive antagonist of the relaxant effects of alpha-CGRP on human temporal artery: comparison with CGRP(8-37).

Authors:  Raphaela Verheggen; Katja Bumann; Alberto J Kaumann
Journal:  Br J Pharmacol       Date:  2002-05       Impact factor: 8.739

4.  CGRP receptors mediating CGRP-, adrenomedullin- and amylin-induced relaxation in porcine coronary arteries. Characterization with 'Compound 1' (WO98/11128), a non-peptide antagonist.

Authors:  P Hasbak; A Sams; S Schifter; J Longmore; L Edvinsson
Journal:  Br J Pharmacol       Date:  2001-08       Impact factor: 8.739

Review 5.  Diencephalic and brainstem mechanisms in migraine.

Authors:  Simon Akerman; Philip R Holland; Peter J Goadsby
Journal:  Nat Rev Neurosci       Date:  2011-09-20       Impact factor: 34.870

6.  Characterization of the structure of RAMP1 by mutagenesis and molecular modeling.

Authors:  John Simms; Debbie L Hay; Mark Wheatley; David R Poyner
Journal:  Biophys J       Date:  2006-04-21       Impact factor: 4.033

Review 7.  The pharmacology of adrenomedullin receptors and their relationship to CGRP receptors.

Authors:  Debbie L Hay; Alex C Conner; Stephen G Howitt; David M Smith; David R Poyner
Journal:  J Mol Neurosci       Date:  2004       Impact factor: 3.444

8.  Calcitonin gene-related peptide (CGRP) antagonists: blockers of neuronal transmission in migraine.

Authors:  Susan D Brain
Journal:  Br J Pharmacol       Date:  2004-07-05       Impact factor: 8.739

9.  Effects of the CGRP receptor antagonist BIBN4096BS on capsaicin-induced carotid haemodynamic changes in anaesthetised pigs.

Authors:  Kapil Kapoor; Udayasankar Arulmani; Jan P C Heiligers; Ingrid M Garrelds; Edwin W Willems; Henri Doods; Carlos M Villalón; Pramod R Saxena
Journal:  Br J Pharmacol       Date:  2003-08-26       Impact factor: 8.739

10.  CL/RAMP2 and CL/RAMP3 produce pharmacologically distinct adrenomedullin receptors: a comparison of effects of adrenomedullin22-52, CGRP8-37 and BIBN4096BS.

Authors:  D L Hay; S G Howitt; A C Conner; M Schindler; D M Smith; D R Poyner
Journal:  Br J Pharmacol       Date:  2003-08-26       Impact factor: 8.739
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