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Kratom Alkaloids, Natural and Semi-Synthetic, Show Less Physical Dependence and Ameliorate Opioid Withdrawal
Cellular and Molecular Neurobiology ( IF 4 ) Pub Date : 2021-01-12 , DOI: 10.1007/s10571-020-01034-7
Lisa L Wilson 1 , Soumen Chakraborty 2 , Shainnel O Eans 1 , Thomas J Cirino 1 , Heather M Stacy 1 , Chloe A Simons 1 , Rajendra Uprety 3 , Susruta Majumdar 2 , Jay P McLaughlin 1
Affiliation  

Chronic administration of opioids produces physical dependence and opioid-induced hyperalgesia. Users claim the Thai traditional tea “kratom” and component alkaloid mitragynine ameliorate opioid withdrawal without increased sensitivity to pain. Testing these claims, we assessed the combined kratom alkaloid extract (KAE) and two individual alkaloids, mitragynine (MG) and the analog mitragynine pseudoindoxyl (MP), evaluating their ability to produce physical dependence and induce hyperalgesia after chronic administration, and as treatments for withdrawal in morphine-dependent subjects. C57BL/6J mice (n = 10/drug) were administered repeated saline, or graded, escalating doses of morphine (intraperitoneal; i.p.), kratom alkaloid extract (orally, p.o.), mitragynine (p.o.), or MP (subcutaneously, s.c.) for 5 days. Mice treated chronically with morphine, KAE, or mitragynine demonstrated significant drug-induced hyperalgesia by day 5 in a 48 °C warm-water tail-withdrawal test. Mice were then administered naloxone (10 mg/kg, s.c.) and tested for opioid withdrawal signs. Kratom alkaloid extract and the two individual alkaloids demonstrated significantly fewer naloxone-precipitated withdrawal signs than morphine-treated mice. Additional C57BL/6J mice made physically dependent on morphine were then used to test the therapeutic potential of combined KAE, mitragynine, or MP given twice daily over the next 3 days at either a fixed dose or in graded, tapering descending doses. When administered naloxone, mice treated with KAE, mitragynine, or MP under either regimen demonstrated significantly fewer signs of precipitated withdrawal than control mice that continued to receive morphine. In conclusion, while retaining some liabilities, kratom, mitragynine, and mitragynine pseudoindoxyl produced significantly less physical dependence and ameliorated precipitated withdrawal in morphine-dependent animals, suggesting some clinical value.



中文翻译:

Kratom 生物碱,天然和半合成,显示较少的身体依赖性和改善阿片类药物戒断

长期服用阿片类药物会产生身体依赖性和阿片类药物诱发的痛觉过敏。用户声称泰国传统茶“kratom”和成分生物碱帽柱木碱可改善阿片类药物戒断,而不会增加对疼痛的敏感性。测试这些说法,我们评估了组合的 kratom 生物碱提取物 (KAE) 和两种单独的生物碱,帽柱木碱 (MG) 和模拟帽柱木碱假吲哚酚 (MP),评估它们在长期给药后产生身体依赖性和诱导痛觉过敏的能力,以及作为治疗戒断吗啡依赖受试者。C57BL/6J 小鼠 ( n = 10/药物)重复给予生理盐水或分级递增剂量的吗啡(腹膜内注射;腹腔注射)、卡痛叶生物碱提取物(口服,口服)、帽柱木碱(口服)或 MP(皮下注射,皮下注射),持续 5 天。长期使用吗啡、KAE 或帽柱木碱治疗的小鼠在第 5 天时在 48 °C 温水退尾试验中表现出显着的药物诱导痛觉过敏。然后给小鼠施用纳洛酮(10 mg/kg,sc)并测试阿片类药物戒断症状。Kratom 生物碱提取物和两种单独的生物碱表现出比吗啡处理的小鼠明显更少的纳洛酮沉淀戒断症状。然后使用额外的 C57BL/6J 小鼠对吗啡产生身体依赖,以测试在接下来的 3 天内每天两次以固定剂量或分级给药的组合 KAE、帽柱木碱或 MP 的治疗潜力,逐渐减少剂量。当给予纳洛酮时,在任一方案下接受 KAE、帽柱木碱或 MP 治疗的小鼠表现出比继续接受吗啡的对照小鼠明显更少的突然戒断迹象。总之,在保留一些负债的同时,卡痛叶、帽柱木碱和帽柱木碱假吲哚酚产生的身体依赖性显着降低,并改善吗啡依赖动物的突然戒断,表明具有一定的临床价值。

更新日期:2021-01-12
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