THE ANTIMIGRAINE DRUG, SUMATRIPTAN (GR43175), SELECTIVELY BLOCKS NEUROGENIC PLASMA EXTRAVASATION FROM BLOOD-VESSELS IN DURA MATER
THE ANTIMIGRAINE DRUG, SUMATRIPTAN (GR43175), SELECTIVELY BLOCKS NEUROGENIC PLASMA EXTRAVASATION FROM BLOOD-VESSELS IN DURA MATER
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DOI：
10.1111/j.1476-5381.1990.tb14679.x
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发表时间：
1990-01-01
影响因子：
7.3
通讯作者：
MOSKOWITZ, MA
中科院分区：
文献类型：
--
作者：
BUZZI, MG;MOSKOWITZ, MA
1. 我们描述了GR43175，一种5-羟色胺（5-HT1）样受体激动剂，在一个重要的疼痛敏感的颅内组织，硬脑膜内神经源性介导的血浆蛋白外渗的作用。2. GR43175可明显减弱同侧硬脑膜血管内125i -白蛋白的外渗作用（100 .mu）。g kg-1)单侧三叉神经电刺激前15分钟（1.2 mA, 5 Hz, 5 ms, 5 min）；受激侧/未受激侧比值由1.81降至1.23，差异有统计学意义（P < 0.005）。3. GR43175（100 .亩）G kg-1，静脉注射，大鼠；30 .mu。在系统辣椒素治疗（0.5或1 μ m）前10分钟注射，与对照相比，放射性标记白蛋白的渗漏从163%减少到119% （P < 0.005，豚鼠）或从174减少到118% （P < 0.05，大鼠）。Mol kg-1，静脉注射)。4. GR43175（30-300 .亩）G kg-1)不能阻断三叉神经支配的大鼠和豚鼠（结膜、眼睑和嘴唇）颅外组织内血浆蛋白的外渗。5. 静脉滴注5-HT （1 .mu）后的蛋白渗漏。GR43175 （100,300 .mu）对介导神经源性血浆外渗漏的神经肽、P物质（0.3 nmol kg-1或1 nmol kg-1）和神经激肽A （1 nmol kg-1）均无阻滞作用。G kg-1)，尽管存在泄漏，其量相当于随后的神经源性刺激。6. GR43175（100 .亩）G kg-1)缓激肽减少(10 .mu。mol kg-1)诱导的外渗率为142% ~ 115% （P < 0.05）。7. 这些结果表明GR43175在硬脑膜血管神经发生机制中的重要作用。由于麦角生物碱具有相似的药物活性，因此建议治疗急性血管性头痛的药物可能具有类似的作用机制。
1. We describe the actions of GR43175, a 5-hydroxytryptamine, (5-HT1)-like receptor agonist, on neurogenically-mediated plasma protein extravasation within an important pain-sensitive intracranial tissue, the dura mater. 2. GR43175 markedly attenuated etravasation of 125I-albumin from blood vessels within ipsilateral dura mater when administered to rats (100 .mu.g kg-1) fifteen minutes before unilateral electrical trigeminal stimulation (1.2 mA, 5 Hz, 5 ms, 5 min.); the ratio (stimulated/unstimulated sides) decreased from 1.81 to 1.23, (P < 0.005). 3. GR43175 (100 .mu.g kg-1, i.v., rats; 30 .mu.g kg-1, i.v., guinea-pigs) decreased the leakage of radiolabelled albumin from 163% to 119% (P < 0.005, guinea-pig) or from 174 to 118% (P < 0.05, rat) above vehicle-treated controls when injected ten minutes before systemic capsaicin treatment (0.5 or 1 .mu.mol kg-1, i.v.). 4. GR43175 (30-300 .mu.g kg-1) did not block plasma protein extravasation within extracranial tissues of rats and guinea-pigs innervated by the trigeminal nerve (conjunctiva, eyelid and lip). 5. The protein leakage which followed the i.v. administration of 5-HT (1 .mu.mol kg-1) or neuropeptides which mediate neurogenic plasma extravasation, substance P (0.3 nmol kg-1 or 1 nmol kg-1) and neurokinin A (1 nmol kg-1), was not blocked by GR43175 (100, 300 .mu.g kg-1) despite the presence of leakage in amounts equivalent to the following neurogenic stimulation. 6. GR43175 (100 .mu.g kg-1) decreased bradykinin (10 .mu.mol kg-1)-induced extravasation from 142 to 115% above vehicle-treated animals (P < 0.05). 7. These results demonstrate an important action of GR43175 on neurogenic mechanisms in dural blood vessels. Since the ergot alkaloids possess a similar profile of drug activity, it is suggested that drugs useful in the treatment of acute vascular headaches may share a similar mechanism of action.