Effect of adjuvant drugs on the analgesic activity of opioid morphine analgesics and compound RU-1205

Q3 Pharmacology, Toxicology and Pharmaceutics
A. Spasov, O. Grechko, N. Eliseeva, Yuliya V. Lifanova, Angelina N. Aleksandrenkova
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引用次数: 0

Abstract

Introduction: Adjuvant medications can be used to increase the analgesic effect of opioid analgesics, reduce the manifestation of side effects, and also for premedication. This paper provides information on the effect of clonidine, haloperidol, metocloparmide, diazepam, midazolam on opioid analgesics: - morphine and the selective kappa-opioid agonist compound RU-1205. Materials and methods: A probable interaction between RU-1205, morphine and adjuvant drugs in pain behaviors was carried out on the model of somatogenic pain. 95 male mice received either RU-1205 (5 mg/kg, i.p.) and morphine (1 mg/kg, i.p.) separately or in combination with haloperidol (0.45 mg/kg, i.p.); midazolam (0.3 mg/kg, i.p.); diazepam (1 mg/kg, i.p.); metoclopramide (5 mg/kg, i.p.), and clonidine (1 mg/kg, i.p.). The analgesic effect was assessed by tail flick test. Registration of the latent period of the reaction was carried out 30, 60 and 90 minutes after the adjuvant drug administration. Results: When studying the interaction with morphine, it was found that clonidine, haloperidol and metoclopramide enhanced the effects; diazepam offset them, and midazolam had no affect on the analgesic properties. In the course of the studies, RU-1205 showed an increase in analgesic activity when combined with clonidine, a slight increase with midazolam, and a decrease when co-administered with diazepam. Haloperidol had no influence on the effect of RU-1205, while metoclopramide both potentiated and reduced the analgesic effect. Discussion: Pharmacodynamic and pharmacokinetic interactions of RU-1205 with an α2AR agonist, benzodiazepine receptor agonists, D2P antagonist, and σ-receptor blocker were established. Conclusion: The presented data make it possible to more accurately formulate ideas about the localization and action mechanism of the kappa-agonist of opioid receptors, the compound RU-1205.
辅助药物对阿片类吗啡镇痛剂及复方RU-1205镇痛活性的影响
前言:辅助用药可增加阿片类镇痛药的镇痛效果,减少副作用的表现,也可用于药物前治疗。本文介绍了氯定、氟哌啶醇、甲氧氯帕胺、地西泮、咪达唑仑对阿片类镇痛药-吗啡和选择性卡帕-阿片类激动剂化合物RU-1205的影响。材料与方法:在体源性疼痛模型上研究RU-1205与吗啡及辅助药物在疼痛行为中的可能相互作用。95只雄性小鼠分别接受RU-1205 (5 mg/kg, i.p)和吗啡(1 mg/kg, i.p)或与氟哌啶醇(0.45 mg/kg, i.p)联合治疗;咪达唑仑(0.3 mg/kg, i.p);安定(1mg /kg, ig);甲氧氯普胺(5mg /kg, i.p),可乐定(1mg /kg, i.p)。采用甩尾试验评价镇痛效果。在给药后30min、60min和90min分别记录反应潜伏期。结果:在与吗啡相互作用的研究中,发现可乐定、氟哌啶醇和甲氧氯普胺增强了其作用;安定抵消了它们,而咪达唑仑对镇痛性质没有影响。在研究过程中,RU-1205与克拉定联用时镇痛活性增加,与咪达唑仑联用时镇痛活性略有增加,与地西泮联用时镇痛活性降低。氟哌啶醇对RU-1205的镇痛作用无影响,而甲氧氯普胺可增强或减弱其镇痛作用。讨论:建立了RU-1205与α2AR激动剂、苯二氮卓受体激动剂、D2P拮抗剂和σ受体阻滞剂的药效学和药动学相互作用。结论:本研究为阿片受体kappa激动剂RU-1205的定位及作用机制的研究提供了更为准确的思路。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Research Results in Pharmacology
Research Results in Pharmacology Medicine-Pharmacology (medical)
CiteScore
1.50
自引率
0.00%
发文量
32
审稿时长
12 weeks
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