特征的降钙素相关基因肽受体拮抗剂telcagepant (mk - 0974)在人类孤立的冠状动脉。

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陈肯塔基州,Edvinsson L Eftekhari年代,Kimblad阿宝,凯恩SA (merrill Lynch) J,哈格里夫斯RJ, de Vries R, Garrelds IM, van den Bogaerdt AJ,在啊,Maassenvandenbrink

特征的降钙素相关基因肽受体拮抗剂telcagepant (mk - 0974)在人类孤立的冠状动脉。

J Exp其他杂志》2010年9月1日,334 (3):746 - 52。doi: 10.1124 / jpet.110.165993。Epub 2010年6月23日。

PubMed ID

20573757 (在PubMed

]

文摘

感觉神经肽降钙素相关基因肽(CGRP怎样)扮演了一个角色在初级头痛、偏头痛和CGRP怎样受体拮抗剂是有效的治疗。CGRP怎样是一个强有力的血管舒张,提高的可能性,其受体拮抗心血管效应。因此,我们调查的影响antimigraine CGRP怎样受体拮抗剂telcagepant (mk - 0974) [N - [(3 r, 6 s) 6 - (2, 3-difluorophenyl) 2-oxo-1 - (2, 2, 2-trifluoroethyl) azepan-3-yl] 4 - (2-oxo-2, 3-dihydro-1H-imidazo [4, 5 b] pyridine-1-yl) piperidine-1-carboxamide]人类孤立的冠状动脉。动脉与不同的内部直径进行了研究,评估潜在的微分效应在冠状血管床。人类alphaCGRP浓度放松反应要大于远端冠状动脉(身份证600 - 1000 microm;E (max) = 83 + / - 7%)比冠状动脉近端(身份证,2 - 3毫米;E (max) = 23 + / - 9%)、冠状动脉移植的心脏(身份证,3 - 5毫米;E (max) = 11 + / - 3%)和冠状动脉小动脉(身份证200 - 300 microm;E (max) = 15 + / - 7%)。Telcagepant本身并不引起冠状血管收缩或放松。 Pretreatment with telcagepant (10 nM to 1 microM) antagonized alphaCGRP-induced relaxation competitively in distal coronary arteries (pA(2) = 8.43 +/- 0.24) and proximal coronary arteries and coronary arterioles (1 microM telcagepant, giving pK(B) = 7.89 +/- 0.13 and 7.78 +/- 0.16, respectively). alphaCGRP significantly increased cAMP levels in distal, but not proximal, coronary arteries, and this was abolished by pretreatment with telcagepant. Immunohistochemistry revealed the expression and colocalization of the CGRP receptor elements calcitonin-like receptor and receptor activity-modifying protein 1 in the smooth muscle cells in the media layer of human coronary arteries. These findings in vitro support the cardiovascular safety of CGRP receptor antagonists and suggest that telcagepant is unlikely to induce coronary side effects under normal cardiovascular conditions.

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药物靶点

药物	目标	类	生物	药理作用	行动
Telcagepant	降钙素相关基因肽1型受体	蛋白质	人类	未知的	不可用	细节