Institute of Pharmacology and Toxicology, Medical Faculty, O. v. Guericke University, Leipziger Str. 44, 30124, Magdeburg, Germany.
Psychopharmacology (Berl). 2014 Jan;231(1):13-25. doi: 10.1007/s00213-013-3201-y. Epub 2013 Jul 12.
Mitragyna speciosa and its extracts are named kratom (dried leaves, extract). It contains several alkaloids and is used in traditional medicine to alleviate musculoskeletal pain, hypertension, coughing, diarrhea, and as an opiate substitute for addicts. Abuse and addiction to kratom is described, and kratom has attracted increasing interest in Western countries. Individual effects of kratom on opioidergic, adrenergic, serotonergic, and dopaminergic receptors are known, but not all of the effects have been explained. Pharmacokinetic and pharmacodynamic data are needed.
The effects of kratom extract on mice behavior were investigated following oral (po), intraperitoneal (ip), and intracerebroventricular (icv) application. Receptor-binding studies were performed.
In μ opioid receptor knockout mice (-/-) and wild type (+/+) animals, the extract reduced locomotor activity after ip and low po doses in +/+ animals, but not after icv administration. The ip effect was counteracted by 0.3 mg/kg of apomorphine sc, suggesting dopaminergic presynaptic activity. An analgesic effect was only found in -/- mice after icv application. Norbinaltorphimine abolished the analgesic effect, but not the inhibitory effect, on locomotor activity, indicating that the analgesic effect is mediated via κ opioid receptors. Oral doses, which did not diminish locomotor activity, impaired the acquisition of shuttle box avoidance learning. There was no effect on consolidation. Binding studies showed affinity of kratom to μ, δ, and κ opioid receptors and to dopamine D1 receptors.
The results obtained in drug-naïve mice demonstrate weak behavioral effects mediated via μ and κ opioid receptors.
美托叶碱树及其提取物被命名为东革阿里（干叶、提取物）。它含有几种生物碱，用于传统医学缓解肌肉骨骼疼痛、高血压、咳嗽、腹泻，并作为吸毒者的阿片类药物替代品。东革阿里的滥用和成瘾已被描述，并且东革阿里在西方国家引起了越来越多的关注。东革阿里对阿片类、肾上腺素能、5-羟色胺能和多巴胺能受体的个体影响已知，但并非所有影响都已得到解释。需要药代动力学和药效学数据。
研究了东革阿里提取物经口服（po）、腹腔内（ip）和脑室内（icv）给药后对小鼠行为的影响。进行了受体结合研究。
在 μ 阿片受体敲除小鼠（-/-）和野生型（+/+）动物中，提取物在 +/+ 动物中降低了 ip 和低 po 剂量后的运动活性，但在 icv 给药后没有降低。ip 效应被 sc 给予 0.3 mg/kg 的阿扑吗啡逆转，表明多巴胺能突触前活性。仅在 icv 应用后，在 -/- 小鼠中才发现镇痛作用。诺布吗啡取消了对运动活性的镇痛作用，但没有取消对运动活性的抑制作用，表明镇痛作用是通过 κ 阿片受体介导的。没有降低运动活性的口服剂量会损害穿梭箱回避学习的获得。对巩固没有影响。结合研究表明东革阿里对 μ、δ 和 κ 阿片受体以及多巴胺 D1 受体具有亲和力。
在未经药物处理的小鼠中获得的结果表明，通过 μ 和 κ 阿片受体介导的行为作用较弱。
