低至中等剂量的3-甲基甲卡西酮(3-MMC)在健康志愿者中产生镇痛作用:一项设计药物的原理证明研究。

IF 3.5 3区 医学 Q2 NEUROSCIENCES
Johannes G Ramaekers, Johannes T Reckweg, Natasha L Mason, Kim Pc Kuypers, Stefan W Toennes, Eef L Theunissen
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引用次数: 0

摘要

3-甲基卡西酮(3-MMC)是一种合成卡西酮,在作为设计药物或“合法兴奋剂”出现在消费市场后,已在许多司法管辖区列入管制名单。目前,合成卡西酮还没有医学上的应用,但在过去,卡西酮和其他与安非他明结构相关的化合物因其内在的镇痛质量而被评价和认可。本研究旨在评估低至中等剂量(25、50和100 mg) 3-MMC对健康志愿者(N = 14)的镇痛作用。在压力疼痛阈值(PPT)和冷压力测试(CPT)范式中,参与者在给药后重复暴露于实验性疼痛长达5小时。采用情绪状态问卷评估3-MMC的主观效果。总体而言,在两种实验疼痛模型中,3-MMC产生了与剂量相关的压力疼痛阈值升高,并减少了主观疼痛和不愉快。3-MMC的镇痛作用在50和100 mg剂量后最为突出,并持续至给药后5小时。3-MMC也产生了剂量相关的情绪增量,在给药后1小时显著,但在给药后5小时不明显。结论是,3-MMC在足够低的剂量下产生持久的镇痛作用,以避免具有挑战性的主观体验,并且与良性副作用有关。目前的数据支持在患者群体中进一步研究低至中剂量3-MMC的镇痛作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Low to moderate doses of 3-methylmethcathinone (3-MMC) produce analgesic effects in healthy volunteers: a proof of principle study with a designer drug.

3-Methylmethcathinone (3-MMC) is a synthetic cathinone that has been scheduled in many jurisdictions after it appeared on the consumer market as a designer drug or "legal high". At present, there are no medical applications for synthetic cathinones, but in the past cathinone and other compounds that are structurally related to amphetamine have been evaluated and recognized for their intrinsic analgesic quality. The present study aimed to assess the analgesic effects of low to moderate doses (25, 50 and 100 mg) of 3-MMC in healthy volunteers (N = 14) in a cross-over, placebo-controlled study. Participants were repeatedly exposed to experimental pain for up to 5 h after dosing in pressure pain threshold (PPT) and cold pressor test (CPT) paradigms. A profile of mood states questionnaire was used to assess the subjective effects of 3-MMC. Overall, 3-MMC produced dose-related elevations in pressure pain threshold and reduced subjective painfulness and unpleasantness in both experimental pain models. The analgesic effects of 3-MMC were most prominent after the 50 and 100 mg dose and persisted consistently for up to 5 h after dosing. 3-MMC also produced dose-related increments in mood that were prominent at 1 h, but not at 5 h after dosing. It is concluded that 3-MMC produces prolonged analgesic effects at doses that appear low enough to avoid a challenging subjective experience and that have been associated with a benign side effect profile. The present data warrant further research into the analgesic effects of low to moderate doses of 3-MMC in patient populations.

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来源期刊
Psychopharmacology
Psychopharmacology 医学-精神病学
CiteScore
7.10
自引率
5.90%
发文量
257
审稿时长
2-4 weeks
期刊介绍: Official Journal of the European Behavioural Pharmacology Society (EBPS) Psychopharmacology is an international journal that covers the broad topic of elucidating mechanisms by which drugs affect behavior. The scope of the journal encompasses the following fields: Human Psychopharmacology: Experimental This section includes manuscripts describing the effects of drugs on mood, behavior, cognition and physiology in humans. The journal encourages submissions that involve brain imaging, genetics, neuroendocrinology, and developmental topics. Usually manuscripts in this section describe studies conducted under controlled conditions, but occasionally descriptive or observational studies are also considered. Human Psychopharmacology: Clinical and Translational This section comprises studies addressing the broad intersection of drugs and psychiatric illness. This includes not only clinical trials and studies of drug usage and metabolism, drug surveillance, and pharmacoepidemiology, but also work utilizing the entire range of clinically relevant methodologies, including neuroimaging, pharmacogenetics, cognitive science, biomarkers, and others. Work directed toward the translation of preclinical to clinical knowledge is especially encouraged. The key feature of submissions to this section is that they involve a focus on clinical aspects. Preclinical psychopharmacology: Behavioral and Neural This section considers reports on the effects of compounds with defined chemical structures on any aspect of behavior, in particular when correlated with neurochemical effects, in species other than humans. Manuscripts containing neuroscientific techniques in combination with behavior are welcome. We encourage reports of studies that provide insight into the mechanisms of drug action, at the behavioral and molecular levels. Preclinical Psychopharmacology: Translational This section considers manuscripts that enhance the confidence in a central mechanism that could be of therapeutic value for psychiatric or neurological patients, using disease-relevant preclinical models and tests, or that report on preclinical manipulations and challenges that have the potential to be translated to the clinic. Studies aiming at the refinement of preclinical models based upon clinical findings (back-translation) will also be considered. The journal particularly encourages submissions that integrate measures of target tissue exposure, activity on the molecular target and/or modulation of the targeted biochemical pathways. Preclinical Psychopharmacology: Molecular, Genetic and Epigenetic This section focuses on the molecular and cellular actions of neuropharmacological agents / drugs, and the identification / validation of drug targets affecting the CNS in health and disease. We particularly encourage studies that provide insight into the mechanisms of drug action at the molecular level. Manuscripts containing evidence for genetic or epigenetic effects on neurochemistry or behavior are welcome.
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