Department of Neurology, Ghent University Hospital, Ghent, Belgium.
Acta Neurol Belg. 2009 Dec;109(4):252-61.
Calcitonin gene-related peptide (CGRP) has a widespread distribution throughout the trigeminovascular system and other brain areas involved in migraine pathogenesis. Serum levels of CGRP are elevated during the migraine attack and return to normal with alleviation of pain. Intravenous injection of CGRP in migraineurs results in delayed headache similar to migraine. Since CGRP receptor antagonists lack direct vasoconstrictor activity, this therapeutic approach may offer advantages over the current mainstay of specific acute migraine treatment with 5-HT1B/1D receptor agonists (triptans), contra-indicated in patients with underlying cardiovascular disease. Intravenous BIBN4096BS (olcegepant) and oral MK-0974 (telcagepant), two CGRP-receptor antagonists, were safe and effective in the treatment of migraine attacks in Phase I and II trials. In a Phase III clinical trial, the efficacy of telcagepant 300 mg was comparable to that of zolmitriptan 5 mg. We intend to review the rationale for the use of CGRP-receptor antagonists, and to outline current developments and future perspectives.
降钙素基因相关肽（CGRP）在三叉血管系统和其他参与偏头痛发病机制的脑区广泛分布。偏头痛发作期间血清 CGRP 水平升高，疼痛缓解后恢复正常。偏头痛患者静脉注射 CGRP 可导致类似偏头痛的延迟性头痛。由于 CGRP 受体拮抗剂没有直接的血管收缩活性，这种治疗方法可能优于目前偏头痛特异性急性治疗的主要方法，即 5-HT1B/1D 受体激动剂（曲普坦类），因为它们在有潜在心血管疾病的患者中是禁忌的。在 I 期和 II 期临床试验中，两种 CGRP 受体拮抗剂，静脉注射 BIBN4096BS（olcegepant）和口服 MK-0974（telcagepant），在治疗偏头痛发作时是安全有效的。在一项 III 期临床试验中，telcagepant 300mg 的疗效与佐米曲普坦 5mg 相当。我们打算回顾使用 CGRP 受体拮抗剂的基本原理，并概述当前的发展和未来的前景。
