Pharmacological profile of BIBN4096BS, the first selective small molecule CGRP antagonist
Pharmacological profile of BIBN4096BS, the first selective small molecule CGRP antagonist
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DOI：
10.1038/sj.bjp.0703110
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发表时间：
2000-02-01
影响因子：
7.3
通讯作者：
Eberlein, W
中科院分区：
文献类型：
--
作者：
Doods, H;Hallermayer, G;Eberlein, W
降钙素基因相关肽（CGRP）是已知最专利的内源性血管扩张剂之一。这种肽在偏头痛发作期间增加，并与偏头痛的发病机制有关。在这里，我们报道了第一个小分子选择性CGRP拮抗剂：BIBN4096BS。在体外，该化合物对灵长类动物的CGRP受体非常有效，对人类CGRP受体的亲和力（K-i）为14.1 +/- 6.3 (n = 4) phl。在体外模型中，BIBN4096BS剂量在1 ~ 30 μ g kg(-1) （i.v）之间，可抑制三叉神经节刺激释放的CGRP对狨猴面部血流的影响。综上所述，BIBN4096BS是一种有效的选择性CGRP拮抗剂。
Calcitonin gene-related peptide (CGRP) is one of the most patent 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 14.1 +/- 6.3 (n = 4) phl. In an in vitro model, BIBN4096BS in doses between 1 and 30 mu g 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.