Goadsby P J, Knight Y E
Institute of Neurology, National Hospital for Neurology and Neurosurgery, London, UK.
Cephalalgia. 1997 May;17(3):153-8. doi: 10.1046/j.1468-2982.1997.1703153.x.
The trigeminovascular system consists of bipolar neurons which innervate pain-sensitive intracranial structures and projecting to neurons in the superficial laminae of the caudal trigeminal nucleus and of the dorsal horns of C1 and C2. The serotonin (5HT1B/D) agonist zolmitriptan (311C90) has been shown to be effective in the treatment of acute attacks of migraine and experimental data suggest that it may have both peripheral and central sites of action. This study sought to further investigate possible central effects of zolmitriptan (311C90) by examining its distribution in the central nervous system. Specific binding of [3H]-zolmitriptan was determined both ex vivo and in vitro in the cat brain. For the ex vivo studies, cats were anaesthetized with halothane and alpha-chloralose (60 mg/kg intraperitoneal). A femoral vein catheter was inserted for injection of the [3H]-zolmitriptan and then 1 h after injection the brain removed. For the in vitro studies fresh frozen brain slices were incubated with labelled and masking concentrations of zolmitriptan. The distribution of [3H]-zolmitriptan was determined using quantitative autoradiographic methods. The in vitro work demonstrated specific binding of [3H]-zolmitriptan in the superficial laminae of the trigeminal nucleus caudalis and dorsal horns of the C1 and C2 cervical spinal cord. The density of binding was 53 +/- 9 fmol/mg for the trigeminal nucleus caudalis, 47 +/- 7 fmol/mg for C1 and 50 +/- 6 fmol/mg for C2. The ex vivo work demonstrated binding in anatomically identical areas which was less dense than that seen with the in vitro method. These data confirm the existence of a population of receptors that specifically bind zolmitriptan following systemic administration. These receptors may, in part, be responsible for its clinical efficacy and reinforce the importance of central trigeminal neurons as a possible site of action of anti-migraine drugs.
三叉神经血管系统由双极神经元组成，这些神经元支配对疼痛敏感的颅内结构，并投射至三叉神经尾侧核浅层以及C1和C2背角的神经元。5-羟色胺（5HT1B/D）激动剂佐米曲普坦（311C90）已被证明可有效治疗偏头痛急性发作，实验数据表明其可能具有外周和中枢作用位点。本研究旨在通过检测佐米曲普坦（311C90）在中枢神经系统中的分布，进一步探究其可能的中枢效应。在猫脑中通过离体和体外实验确定了[3H] - 佐米曲普坦的特异性结合。对于离体研究，用氟烷和α - 氯醛糖（60mg/kg腹腔注射）麻醉猫。插入股静脉导管用于注射[3H] - 佐米曲普坦，注射后1小时取出大脑。对于体外研究，将新鲜冷冻的脑片与标记和非标记浓度的佐米曲普坦一起孵育。使用定量放射自显影方法确定[3H] - 佐米曲普坦的分布。体外实验表明[3H] - 佐米曲普坦在三叉神经尾侧核浅层以及C1和C2颈脊髓背角有特异性结合。三叉神经尾侧核的结合密度为53±9fmol/mg，C1为47±7fmol/mg，C2为50±6fmol/mg。离体实验表明在解剖学上相同的区域有结合，但密度低于体外实验所见。这些数据证实了全身给药后存在特异性结合佐米曲普坦的受体群体。这些受体可能部分地解释了其临床疗效，并强化了中枢三叉神经元作为抗偏头痛药物可能作用位点的重要性。
