摘要
背景:合成永久性阿片类药物的主要目的是确保它们不会进入中枢神经系统。这类药物可以提供镇痛活性,减少对中枢神经系统的镇静作用和其它副作用。 方法:我们进行了同行评议研究文献的书目数据库搜索,并总结了我们在这一领域的发表结果。 结果:本综述重点介绍了通过各种物理化学方法,体外以及体内试验表征永久性阿片类药物。阿片类生物碱的碱性和亲脂性在微观,物种特定水平上进行讨论。阿片类药物的葡萄糖醛酸苷结合物也被综述。尽管主要代谢物吗啡-3-葡萄糖醛酸苷不以高亲和力与阿片受体结合,但吗啡-6-葡萄糖醛酸苷是一种有效的镇痛药,至少部分是由于其出乎意料的高亲脂性。我们讨论了永久性正电荷的季铵阿片衍生物,详细描述了它们在各种体内动物试验和体外研究中的抗感受伤害活性和对胃肠动力的影响。还评论了具有拮抗活性的化合物。我们研究的最后一部分集中在硫酸盐结合物的吗啡衍生物,显示独特的药理学性质,因为他们在人体的任何pH值带负电荷。 结论:总之,这次审查的结果证实了永久性阿片类药物在药理学研究领域的重要性。
关键词: 永久性带电阿片类药物,体外和体内试验,碱性,亲脂性,葡萄糖醛酸结合物,中枢神经系统,季铵阿片衍生物,硫酸酯结合物。
Current Medicinal Chemistry
Title:Physicochemical and Pharmacological Characterization of Permanently Charged Opioids
Volume: 24 Issue: 33
关键词: 永久性带电阿片类药物,体外和体内试验,碱性,亲脂性,葡萄糖醛酸结合物,中枢神经系统,季铵阿片衍生物,硫酸酯结合物。
摘要: Background: The main aim of synthesizing permanently charged opioids is to ensure that they do not enter the central nervous system. Such drugs can provide analgesic activity with reduced sedation and other side effects on the central nervous system.
Methods: We undertook a search of bibliographic databases for peer-reviewed research literature and also summarized our published results in this field.
Results: The present review focuses on the characterization of permanently charged opioids by various physicochemical methods, and in vitro as well as in vivo tests. The basicity and lipophilicity of opioid alkaloids are discussed at the microscopic, speciesspecific level. Glucuronide conjugates of opioids are also reviewed. Whereas the primary metabolite morphine-3-glucuronide does not bind to opioid receptors with high affinity, morphine-6-glucuronide is a potent analgesic, at least, partly due to its unexpectedly high lipophilicity. We discuss the quaternary ammonium opioid derivatives of a permanent positive charge, detailing their antinociceptive activity and effects on gastrointestinal motility in various in vivo animal tests and in vitro studies. Compounds with antagonistic activity are also reviewed. The last part of our study concentrates on sulfate conjugates of morphine derivatives that display unique pharmacological properties because they carry a negative charge at any pH value in the human body.
Conclusion: In conclusion, the findings of this review confirm the importance of permanently charged opioids in the investigated fields of pharmacology.
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Cite this article as:
Physicochemical and Pharmacological Characterization of Permanently Charged Opioids, Current Medicinal Chemistry 2017; 24 (33) . https://dx.doi.org/10.2174/0929867324666170705112239
DOI https://dx.doi.org/10.2174/0929867324666170705112239 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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