Olcegepant hydrochloride (BIBN-4096 hydrochloride) 是高效选择性的降钙素基因相关肽 (CGRP) 的拮抗剂, 对人类CGRP的 K_i 值为 14.4 pM。

Olcegepant hydrochloride (BIBN-4096 hydrochloride) is a potent and selective non-peptide antagonist of the calcitonin gene-related peptide 1 (CGRP1) receptor with IC 50 of 0.03 nM and with a K i of 14.4 pM for human CGRP.

Solid

IC50: 0.03 nM (CGRP1)
Ki: 14.4 pM (hCGRP)

Olcegepant possesses higher affinity for the human CGRP receptor than the endogenous ligand CGRP and 150-fold higher affinity compared to the peptidic antagonist CGRP8-37. Olcegepant reverses CGRP-mediated vasodilation in human cerebral vessels and inhibits neurogenic vasodilation in a surrogate animal model of migraine pathophysiology. Olcegepant (BIBN4096BS) is extremely potent at primate CGRP receptors exhibiting an affinity (Ki) for human CGRP receptors of 14.4±6.3 (n=4) pM. Several lines of evidence suggest that a calcitonin-gene related peptide (CGRP) receptor antagonist may serve as a novel abortive migraine treatment. Olcegepant (BIBN4096BS) exhibits competitive antagonism at the CGRP receptor present in SK-N-MC cells. Isolated human cerebral, coronary, and omental arteries are studied with a sensitive myograph technique. CGRP induces a concentration-depende

Olcegepant (BIBN4096BS) in doses between 1 and 30 μg/kg (i.v.) inhibits the effects of CGRP, released by stimulation of the trigeminal ganglion, on facial blood flow in marmoset monkeys. Pre-treatment with Olcegepant (900 μg/kg) inhibits the capsaicin-induced expression of Fos throughout the spinal trigeminal nucleus by 57%. In contrast, the expression of phosphorylated extracellular signal-regulated kinase in the trigeminal ganglion is not changed by Olcegepant pre-treatment. Olcegepant (0.3 to 0.9 mg/kg, i.v.) markedly reduces mechanical allodynia in CCI-ION rats. Olcegepant (0.6 mg/kg, i.v.) significantly reduces the number of c-Fos immunolabeled cells in spinal nucleus of the trigeminal nerve and upregulation of ATF3 transcript (a marker of neuron injury) but not that of interleukin-6 in trigeminal ganglion of CCI-ION rats.

Room temperature in continental US; may vary elsewhere.

4°C, stored under nitrogen In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)

[1]. Rudolf K, et al. Development of human calcitonin gene-related peptide (CGRP) receptor antagonists. 1. Potent and selective small molecule CGRP antagonists. 1-[N2-[3,5-dibromo-N-[[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]carbonyl]-D-tyrosyl]-
[2]. Edvinsson L, et al. Effect of the CGRP receptor antagonist BIBN4096BS in human cerebral, coronary and omentalarteries and in SK-N-MC cells. Eur J Pharmacol. 2002 Jan 2;434(1-2):49-53.

In Vitro: DMSO : 100 mg/mL (110.36 mM; Need ultrasonic)H₂O : ≥ 66.66 mg/mL (73.57 mM)