| Description | Olcegepant (BIBN-4096) is an effective and selective non-peptide calcitonin gene-related peptide 1 (CGRP1) receptor antagonist (IC50 of 0.03 nM and Ki of 14.4 pM for human CGRP). |
| In vitro | Olcegepant在灵长类动物的CGRP受体上显示出极高的效力，对人类CGRP受体的亲和力（Ki）为14.4±6.3 (n=4) pM。该化合物对人类CGRP受体的亲和力高于内源性配体CGRP，并且比肽类拮抗剂CGRP8-37高出150倍。CGRP会引起浓度依赖性的松弛作用，而Olcegepant以竞争性方式对此起拮抗作用。Olcegepant能逆转CGRP介导的人脑血管舒张，并且在偏头痛病理生理学的替代动物模型中抑制神经源性血管舒张。多条证据表明，钙素基因相关肽（CGRP）受体拮抗剂可能作为一种新型的中断性偏头痛治疗方法。Olcegepant在SK-N-MC细胞中表现出对CGRP受体的竞争性拮抗作用。研究中使用灵敏的肌动图技术对人类脑动脉、冠状动脉和网膜动脉进行了单独测试[1][2][3]。 |
| In vivo | 用Olcegepant (900 μg/kg) 预处理可抑制Capsaicin 诱导脊髓三叉神经核内Fos表达的57%。Olcegepant预处理不改变三叉神经节内磷酸化的细胞外信号调节激酶的表达。Olcegepant以1至30 μg/kg (i.v.)的剂量抑制了通过刺激三叉神经节释放的CGRP对狨猴面部血流的影响。Olcegepant (0.3至0.9 mg/kg, i.v.) 显著降低CCI-ION大鼠的机械性痛觉过敏。Olcegepant (0.6 mg/kg, i.v.) 显著减少了CCI-ION大鼠三叉神经核内的c-Fos免疫标记细胞数量并上调了ATF3转录物（神经元损伤的标志）但不是白细胞介素-6的表达[2][4][5]。 |
| Target activity | CGRP1:0.03 nM, CGRP (human):14.4 pM (ki) |
| Synonyms | BIBN-4096, BIBN 4096BS |
| molecular weight | 869.65 |
| Molecular formula | C38H47Br2N9O5 |
| CAS | 204697-65-4 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| Solubility | DMSO: 23.81 mg/mL (27.38 mM), Sonication is recommended. |
| References | 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]-l-lysyl]-4-(4-pyridinyl)piperazine: the first CGRP antagonist for clinical trials in acute migraine. J Med Chem. 2005 Sep 22;48(19):5921-31. 2. Doods H, et al. Pharmacological profile of BIBN4096BS, the first selective small molecule CGRP antagonist. Br J Pharmacol. 2000 Feb;129(3):420-3. 3. 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. 4. Sixt ML, et al. Calcitonin gene-related peptide receptor antagonist Olcegepant acts in the spinal trigeminal nucleus. Brain. 2009 Nov;132(Pt 11):3134-41. 5. Michot B, et al. Differential effects of calcitonin gene-related peptide receptor blockade by Olcegepant on mechanical allodynia induced by ligation of the infraorbital nerve vs the sciatic nerve in the rat. Pain. 2012 Sep;153(9):1939-48. |