• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Pharmacology, Biochemistry and Behavior >Antinociceptive activity of derivatives of improgran and burimamide.
【24h】

Antinociceptive activity of derivatives of improgran and burimamide.

机译：improgran和burimamide衍生物的抗伤害感受活性。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Improgan, a compound related to H2 and H3 antagonists, induces antinociception in rodents after intraventricular administration. Characteristics of improgan and its congeners include: (a) morphine-like antinociception on thermal and mechanical tests in two species; (b) no impairment of motor coordination or locomotor activity; (c) evidence for a novel, nonopioid mechanism that is independent of known histamine receptors; (d) lack of tolerance with daily dosing; and (e) unique structure-activity relationships (SARs). Presently, the antinociceptive activity of several new derivatives of improgan was investigated in rats. Among compounds similar to burimamide, VUF4577 (possessing a two-carbon side chain) and VUF4582 (an N-phenyl derivative of VUF4577) induced complete, dose- and time-dependent antinociception on the hot-plate and tail-flick tests with no behavioral side effects. These compounds (with ED50 values of 71-117 nmol) were approximately twice as potent as burimamide itself (a four-carbon derivative). Two other derivatives in which the thiourea group (C=S, known to cause human toxicity) was replaced by either nitroethene (C=CH-NO2, VUF5405) or urea (C=O, VUF5407) also showed effective, potent antinociception on both assays. The latter compound is the most potent improgan-like drug discovered to date (ED50 = 71 nmol). Furthermore, positional isomers of antinociceptive compounds either lacked activity (VUF5394) or induced toxicity (VUF5393), revealing a high degree of pharmacological specificity. Although the mechanism of improgan antinociception remains unknown, the present results show promise for the further development of safe, effective, and potent pain-relieving compounds.
机译：Improgan是与H2和H3拮抗剂相关的化合物，在室内给药后可诱导啮齿动物产生抗伤害感受。 Improgan及其同类物的特征包括：（a）在两个物种的热力学和机械测试中均表现出类似吗啡的镇痛作用; （b）不损害运动协调能力或运动能力; （c）证据表明一种新颖的非阿片类药物机制独立于已知的组胺受体; （d）每日剂量缺乏耐受性; （e）独特的构效关系（SAR）。目前，在大鼠中研究了几种新的improgan衍生物的抗伤害感受活性。在类似于burimamide的化合物中，VUF4577（具有两个碳的侧链）和VUF4582（VUF4577的N-苯基衍生物）在热板和甩尾试验中诱导完全，剂量和时间相关的镇痛作用，无行为副作用。这些化合物（ED50值为71-117 nmol）的效力大约是burimamide本身（四碳衍生物）的两倍。另外两个衍生物中的硫脲基团（C = S，已知会引起人的毒性）被硝基乙烯（C = CH-NO2，VOF5405）或尿素（C = O，VOF5407）取代，这两种衍生物在两种药物上均显示出有效的，有效的镇痛作用分析。后一种化合物是迄今为止发现的最有效的即席类药​​物（ED50 = 71 nmol）。此外，抗伤害感受性化合物的位置异构体缺乏活性（VUF5394）或诱导毒性（VUF5393），显示出高度的药理学特异性。尽管促进抗伤害感受的机制尚不清楚，但目前的结果表明有望进一步开发安全，有效和有效的止痛化合物。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号