Evaluation of the antinociceptive activities of several sodium channel blockers using veratrine test in mice

Yoshizawa Kazumi; Arai Narumaki; Suzuki Yukina; Nakamura Toka; Takeuchi Kota; Sakamoto Reinii; Masuda Ritsuko

摘要

Abstract >An important role of voltage‐gated sodium channels (VGSCs) in many different pain states has been established in animal models and humans wherein sodium channel blockers partially ameliorate pain. However, behavioral tests for screening analgesics that exhibit pharmacologic action by acting on VGSCs are rarely reported, and there are no studies on antinociception using veratrine as a nociceptive agent. The aim of the present study was to examine the amount of nociceptive behavior evoked by subcutaneous administration of veratrine into the hind paw and investigate whether veratrine can be used as a VGSC agonist to test the pharmacological properties of candidate analgesics via sodium channel blockade. We report for the first time that intraplantar injection of veratrine produced a reproducible nociceptive response in mice. Furthermore, several sodium channel blockers, namely carbamazepine, valproate, mexiletine, and the selective Nav1.7 inhibitor PF‐04856264, but not flecainide or pilsicainide, reduced veratrine‐induced nociception. In contrast, calcium channel blockers gabapentin and ethosuximide did not change veratrine‐induced nociception. The veratrine test in mice might be a useful tool, at least in part, to evaluate the potential analgesic effect of sodium channel blockers. </abstract> </span> <span class="z_kbtn z_kbtnclass hoverxs" style="display: none;">展开▼</span> </div> <div class="translation abstracttxt"> <span class="zhankaihshouqi fivelineshidden" id="abstract"> <span>机译：</span><Abstract Type =“Main”XML：ID =“Syn22056-Abs-0001”XML：Lang =“en”> <标题类型=“main”>抽象</ title> >电压门控钠的重要作用在动物模型和人体中建立了许多不同疼痛状态的频道（VGSCs），其中钠通道阻滞剂部分改善疼痛。然而，很少报道用于通过作用于VGSC表现出药理学作用的筛选药物的行为试验，并且对使用Veratrine作为伤害剂的抗睡眠性没有研究。本研究的目的是检查通过皮下施用的伤害肌脂碱进入后爪的伤害性行为的量，并研究Veratrine是否可以用作VGSC激动剂，以通过钠通道阻断测试候选镇痛药的药理性质。我们首次报告的是，孕孕丙胺注射术治疗小鼠的可重复性的伤害反应。此外，几种钠通道阻滞剂，即卡巴马嗪，戊酸酯，甘石，和选择性Nav1.7抑制剂PF-04856264，但不是氨砂质或毛虫，降低了藜碱诱导的伤害伤害。相比之下，钙通道阻滞剂加巴彭素和乙杂菊酯没有改变藜碱诱导的伤害效果。小鼠的尿酸盐测试可能是一种有用的工具，至少部分地评估钠通道阻滞剂的潜在镇痛作用。</ p> </摘要> </span> <span class="z_kbtn z_kbtnclass hoverxs" style="display: none;">展开▼</span> </div> </div> <div class="record"> <h2 class="all_title" id="enpatent33" >著录项</h2> <ul> <li> <span class="lefttit">来源</span> <div style="width: 86%;vertical-align: text-top;display: inline-block;"> <a href='/journal-foreign-28762/'>《Synapse》</a> <b style="margin: 0 2px;">|</b><span>2018年第10期</span><b style="margin: 0 2px;">|</b><span>共8页</span> </div> </li> <li> <div class="author"> <span class="lefttit">作者</span> <p id="fAuthorthree" class="threelineshidden zhankaihshouqi"> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Yoshizawa Kazumi&option=202" target="_blank" rel="nofollow">Yoshizawa Kazumi;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Arai Narumaki&option=202" target="_blank" rel="nofollow">Arai Narumaki;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Suzuki Yukina&option=202" target="_blank" rel="nofollow">Suzuki Yukina;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Nakamura Toka&option=202" target="_blank" rel="nofollow">Nakamura Toka;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Takeuchi Kota&option=202" target="_blank" rel="nofollow">Takeuchi Kota;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Sakamoto Reinii&option=202" target="_blank" rel="nofollow">Sakamoto Reinii;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Masuda Ritsuko&option=202" target="_blank" rel="nofollow">Masuda Ritsuko;</a> </p> <span class="z_kbtnclass z_kbtnclassall hoverxs" id="zkzz" style="display: none;">展开▼</span> </div> </li> <li> <div style="display: flex;"> <span class="lefttit">作者单位</span> <div style="position: relative;margin-left: 3px;max-width: 639px;"> <div class="threelineshidden zhankaihshouqi" id="fOrgthree"> <p>Laboratory of Pharmacology and Therapeutics Faculty of Pharmaceutical SciencesTokyo University of ScienceNoda Japan;</p> <p>Laboratory of Pharmacology and Therapeutics Faculty of Pharmaceutical SciencesTokyo University of ScienceNoda Japan;</p> <p>Laboratory of Pharmacology and Therapeutics Faculty of Pharmaceutical SciencesTokyo University of ScienceNoda Japan;</p> <p>Laboratory of Pharmacology and Therapeutics Faculty of Pharmaceutical SciencesTokyo University of ScienceNoda Japan;</p> <p>Laboratory of Pharmacology and Therapeutics Faculty of Pharmaceutical SciencesTokyo University of ScienceNoda Japan;</p> <p>Department of AnesthesiologyTokai University Hachioji HospitalTokyo Japan;</p> <p>Department of AnesthesiologyTokai University Hachioji HospitalTokyo Japan;</p> </div> <span class="z_kbtnclass z_kbtnclassall hoverxs" id="zhdw" style="display: none;">展开▼</span> </div> </div> </li> <li > <span class="lefttit">收录信息</span> <span style="width: 86%;vertical-align: text-top;display: inline-block;"></span> </li> <li> <span class="lefttit">原文格式</span> <span>PDF</span> </li> <li> <span class="lefttit">正文语种</span> <span>eng</span> </li> <li> <span class="lefttit">中图分类</span> <span><a href="https://www.zhangqiaokeyan.com/clc/200.html" title="神经病学与精神病学">神经病学与精神病学;</a></span> </li> <li class="antistop"> <span class="lefttit">关键词</span> <p style="width: 86%;vertical-align: text-top;"> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=mouse&option=203" rel="nofollow">mouse;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=nociception&option=203" rel="nofollow">nociception;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=sodium channel blockers&option=203" rel="nofollow">sodium channel blockers;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=veratrine&option=203" rel="nofollow">veratrine;</a> </p> <div class="translation"> 机译：小鼠;伤害;钠通道阻滞剂;藜; </div> </li> </ul> </div> </div> <div class="literature cardcommon"> <div class="similarity "> <h3 class="all_title" id="enpatent66">相似文献</h3> <div class="similaritytab clearfix"> <ul> <li class="active" >外文文献</li> <li 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The ALLHAT Officers and Coordinators for the ALLHA</a> <span> <a href="/journal-cn-6753/" target="_blank" rel="nofollow" class="tuijian_authcolor"> . 美国医学会杂志：中文版 </a> </span> <span> . 2003</span><span>,第001期</span> </span> </div> </li> <li> <div> <b>3. </b><a class="enjiyixqcontent" href="/academic-journal-cn_chinese-journal-antibiotics_thesis/0201241750429.html">头孢哌酮钠/三唑巴坦钠不同配比复方制剂的体内、外抗菌活性试验及小鼠毒性研究</a> <b>[J]</b> <span> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=张淑华&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor"> . 张淑华</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=王昉彤&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">,王昉彤</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=欧真容&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">,欧真容</a> <span> <a href="/journal-cn-6415/" target="_blank" rel="nofollow" class="tuijian_authcolor"> . 中国抗生素杂志 </a> </span> <span> . 2004</span><span>,第003期</span> </span> </div> </li> <li> <div> <b>4. </b><a class="enjiyixqcontent" href="/academic-journal-cn_foreign-medicine-synthetic-drugs-biochemical-medicine-preparation-volume_thesis/0201267281279.html">阻滞剂与钙通道阻滞剂合用抗心绞痛的利弊评价</a> <b>[J]</b> <span> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=刘泽培&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor"> . 刘泽培</a> <span> <a href="/journal-cn-50956/" target="_blank" rel="nofollow" class="tuijian_authcolor"> . 国外医药：合成药．生化药．制剂分册 </a> </span> <span> . 1990</span><span>,第003期</span> </span> </div> </li> <li> <div> <b>5. </b><a class="enjiyixqcontent" href="/academic-journal-cn_acta-medicinae-universitatis-scientiae-technologiae-huazhong_thesis/0201245893812.html">表达心脏SCN5A基因的人胚肾细胞钠电流特性及其对钠通道阻滞剂的反应性</a> <b>[J]</b> <span> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=刘洋&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor"> . 刘洋</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Hector Barajas-Martinez&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">,Hector Barajas-Martinez</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=阮磊&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">,阮磊</a> <span> <a href="/journal-cn-6547/" target="_blank" rel="nofollow" class="tuijian_authcolor"> . 华中科技大学学报（医学版） </a> </span> <span> . 2013</span><span>,第001期</span> </span> </div> </li> <li> <div> <b>6. </b><a class="enjiyixqcontent" href="/academic-conference-cn_meeting-7162_thesis/020221870953.html">钠通道阻滞剂对早复极心电图的影响</a> <b>[C]</b> <span> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=黄织春&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor"> . 黄织春</a> <span> <a href="/conference-cn-7162/" target="_blank" rel="nofollow" class="tuijian_authcolor"> . 2012年中国心电学论坛 </a> <span> <span> . 2012</span> </span> </div> </li> <li> <div> <b>7. </b><a class="enjiyixqcontent" href="/academic-degree-domestic_mphd_thesis/0203139904.html">含α-氨基酰胺结构的新型钠通道阻滞剂的设计合成及筛选</a> <b>[A] </b> <span> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=李浩田&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor"> . 李浩田</a> <span> . 2016</span> </span> </div> </li> </ul> <ul style="display: none;"> <li> <div> <b>1. </b><a class="enjiyixqcontent" href="/patent-detail/061201676383.html">化学和代谢稳定的具有钠通道阻滞剂活性的二肽</a> <b>[P]</b> . <span> 中国专利： CN103687488B </span> <span> . 2015.06.10</span> </div> </li> <li> <div> <b>2. </b><a class="enjiyixqcontent" href="/patent-detail/06120102885820.html">化学和代谢稳定的具有强效钠通道阻滞剂活性的二肽</a> <b>[P]</b> . <span> 中国专利： CN103687488A </span> <span> . 2014-03-26</span> </div> </li> <li> <div> <b>3. </b><a class="enjiyixqcontent" href="/patent-detail/06130429207142.html">DRUG COMPOUNDS WITH TWO KOVALENT-LINKED SUBSTANCES (SODIUM CHANNEL BLOCKER / P2Y2 RECEPTOR AGONIST) FOR THE TREATMENT OF MICE</a> <b>[P]</b> . <span> 外国专利：  DE60038449T2 </span> <span> . 2009-04-09</span> </div> <p class="zwjiyix translation" style="max-width: initial;height: auto;word-break: break-all;white-space: initial;text-overflow: initial;overflow: initial;"> <span>机译：含两个可价联物质的药物化合物（钠通道阻断剂/ P2Y2受体激动剂），用于治疗小鼠 </span> </p> </li> <li> <div> <b>4. </b><a class="enjiyixqcontent" href="/patent-detail/06130432613990.html">DRUG COMPOUNDS WITH TWO KOVALENT-LINKED SUBSTANCES (SODIUM CHANNEL BLOCKER / P2Y2 RECEPTOR AGONIST) FOR THE TREATMENT OF MICE</a> <b>[P]</b> . <span> 外国专利：  AT390414T </span> <span> . 2008-04-15</span> </div> <p class="zwjiyix translation" style="max-width: initial;height: auto;word-break: break-all;white-space: initial;text-overflow: initial;overflow: initial;"> <span>机译：含两个可价联物质的药物化合物（钠通道阻断剂/ P2Y2受体激动剂），用于治疗小鼠 </span> </p> </li> <li> <div> <b>5. </b><a class="enjiyixqcontent" href="/patent-detail/06130437794324.html">The test of high efficiency on the basis of mamu00ecferas cells for the determination of the profile and the selection of putativos modulators of epithelial sodium channel.Methods of monitoring the activity of an epithelial sodium channel, and to identify a compound modulator of salty taste, a compound that modulates hENaC, and a modulator of human ENaC, and oocyte</a> <b>[P]</b> . <span> 外国专利：  BRPI0412471A </span> <span> . 2006-09-19</span> </div> <p class="zwjiyix translation" style="max-width: initial;height: auto;word-break: break-all;white-space: initial;text-overflow: initial;overflow: initial;"> <span>机译：在哺乳动物细胞基础上进行的高效测试，用于确定上皮钠通道的分布和选择腐烂调节剂。监测上皮钠通道活性的方法，并确定复合的咸味调节剂，调节hENaC的化合物，人类ENaC的调节剂和卵母细胞 </span> </p> </li> </ul> </div> </div> </div> <div class="theme cardcommon" style="overflow: auto;display:none"> <h3 class="all_title" id="enpatent55">相关主题</h3> <ul id="subject"> </ul> </div> </div> </div> </div> <div class="right rightcon"> <div class="details_img cardcommon clearfix" 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