University of Copenhagen, Copenhagen, Denmark.
Cephalalgia. 2011 Apr;31(6):748-50. doi: 10.1177/0333102411398403. Epub 2011 Mar 7.
The calcitonin gene-related peptide (CGRP) receptor antagonists olcegepant and telcagepant are very potent drugs. Both are effective in migraine but in doses much higher than would be predicted from receptor binding and other in vitro results. This could perhaps suggest an effect of CGRP antagonists behind the blood-brain barrier (BBB), i.e. in the central nervous system (CNS).
Comparison of doses needed for CGRP blocking effect in vitro with dose needed in vivo in man and monkeys. Discussion of these doses in relation to doses needed for anti-migraine activity.
In vivo studies in monkeys and man showed that high doses compared to doses needed in vitro are needed to block capsaicin-induced in skin blood flow, a CGRP-mediated reaction. These doses are close to those needed for anti-migraine activity.
The apparently high doses of CGRP receptor antagonists, olcegepant and telcagepant needed for anti-migraine effect are not so high after all. They do not allow a conclusion as to whether CGRP antagonists act on peripheral sites or central sites in migraine.
降钙素基因相关肽（CGRP）受体拮抗剂 olcegepant 和 telcagepant 是非常有效的药物。两者在偏头痛中都有效，但剂量远高于受体结合和其他体外结果所预测的剂量。这可能表明 CGRP 拮抗剂在血脑屏障（BBB）之后起作用，即在中枢神经系统（CNS）中。
比较体外 CGRP 阻断作用所需剂量与体内在人和猴子中所需剂量。讨论这些剂量与抗偏头痛活性所需剂量的关系。
在猴子和人体内的体内研究表明，与体外所需剂量相比，需要高剂量来阻断辣椒素诱导的皮肤血流，这是一种 CGRP 介导的反应。这些剂量接近抗偏头痛活性所需的剂量。
抗偏头痛作用所需的降钙素基因相关肽受体拮抗剂 olcegepant 和 telcagepant 的高剂量实际上并不高。它们并不能得出 CGRP 拮抗剂是在外周部位还是在偏头痛的中枢部位起作用的结论。
