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第二代合成卡西酮对甲基苯丙胺训练大鼠的辨别性刺激作用。

Discriminative-stimulus effects of second generation synthetic cathinones in methamphetamine-trained rats.

作者信息

Naylor Jennifer E, Freeman Kevin B, Blough Bruce E, Woolverton William L, Huskinson Sally L

机构信息

Division of Neurobiology and Behavior Research, Department of Psychiatry and Human Behavior, The University of Mississippi Medical Center, Jackson, MS 39216, United States.

Division of Neurobiology and Behavior Research, Department of Psychiatry and Human Behavior, The University of Mississippi Medical Center, Jackson, MS 39216, United States.

出版信息

Drug Alcohol Depend. 2015 Apr 1;149:280-4. doi: 10.1016/j.drugalcdep.2015.02.002. Epub 2015 Feb 11.

Abstract

BACKGROUND

Synthetic cathinones are beta-ketophenethylamine analogs manufactured to avoid legal restrictions placed on illicit stimulants like methamphetamine. Regulating these "emerging" designer drugs require scientific evidence of abuse potential.

METHODS

The present study evaluated the discriminative-stimulus effects of three synthetic cathinones, recently identified in commercial and confiscated products, in male Sprague-Dawley rats trained to discriminate methamphetamine (1.0 mg/kg) from saline under a fixed-ratio (FR) 20 schedule of food delivery. Three synthetic cathinones, 4-methyl-N-ethylcathinone (4-MEC; 1.0-8.0 mg/kg), 4-methyl-alpha-pyrrolidinopropiophenone (4-MePPP; 4.0-16.0 mg/kg), and alpha-pyrrolidinopentiophenone (alpha-PVP; 0.25-2.0 mg/kg) were tested for their ability to substitute for methamphetamine.

RESULTS

Full substitution for the training dose of methamphetamine occurred at the highest doses for both 4-MePPP and alpha-PVP, and 4-MEC did not substitute at any dose tested.

CONCLUSIONS

The present findings show that two synthetic cathinones, 4-MePPP and alpha-PVP, produced subjective effects similar to those of methamphetamine. The synthetic cathinone, 4-MEC, did not produce subjective effects similar to those of methamphetamine with the parameters used in the current experiment. Based on findings here and by others, these three compounds warrant further tests of abuse potential.

摘要

背景

合成卡西酮是β-酮苯乙胺类似物,其制造目的是规避对甲基苯丙胺等非法兴奋剂的法律限制。对这些“新型”设计药物进行监管需要有滥用潜力的科学证据。

方法

本研究评估了最近在商业产品和没收产品中发现的三种合成卡西酮对雄性斯普拉格-道利大鼠的辨别刺激效应,这些大鼠在固定比率(FR)20的食物递送时间表下接受训练,以区分甲基苯丙胺(1.0毫克/千克)和生理盐水。测试了三种合成卡西酮,4-甲基-N-乙基卡西酮(4-MEC;1.0 - 8.0毫克/千克)、4-甲基-α-吡咯烷丙苯酮(4-MePPP;4.0 - 16.0毫克/千克)和α-吡咯烷戊苯酮(α-PVP;0.25 - 2.0毫克/千克)替代甲基苯丙胺的能力。

结果

4-MePPP和α-PVP在最高剂量时完全替代了训练剂量的甲基苯丙胺,而4-MEC在任何测试剂量下均未产生替代作用。

结论

本研究结果表明,两种合成卡西酮,4-MePPP和α-PVP,产生的主观效应与甲基苯丙胺相似。在当前实验所使用的参数下,合成卡西酮4-MEC未产生与甲基苯丙胺相似的主观效应。基于本研究及其他研究的结果,这三种化合物值得进一步进行滥用潜力测试。

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本文引用的文献

1
'Second-generation' mephedrone analogs, 4-MEC and 4-MePPP, differentially affect monoamine transporter function.
Neuropsychopharmacology. 2015 May;40(6):1321-31. doi: 10.1038/npp.2014.325. Epub 2014 Dec 15.
2
Discriminative and locomotor effects of five synthetic cathinones in rats and mice.
Psychopharmacology (Berl). 2015 Apr;232(7):1197-205. doi: 10.1007/s00213-014-3755-3. Epub 2014 Oct 5.
3
Hybrid dopamine uptake blocker-serotonin releaser ligands: a new twist on transporter-focused therapeutics.
ACS Med Chem Lett. 2014 Apr 15;5(6):623-7. doi: 10.1021/ml500113s. eCollection 2014 Jun 12.
4
Predicting abuse potential of stimulants and other dopaminergic drugs: overview and recommendations.
Neuropharmacology. 2014 Dec;87:66-80. doi: 10.1016/j.neuropharm.2014.03.009. Epub 2014 Mar 22.
6
Pharmacology of novel synthetic stimulants structurally related to the "bath salts" constituent 3,4-methylenedioxypyrovalerone (MDPV).
Neuropharmacology. 2014 Dec;87:206-13. doi: 10.1016/j.neuropharm.2014.02.016. Epub 2014 Mar 2.
7
The analytical investigation of synthetic street drugs containing cathinone analogs.
Forensic Sci Int. 2014 Jan;234:50-6. doi: 10.1016/j.forsciint.2013.08.021. Epub 2013 Sep 19.
8
Monoamine transporter and receptor interaction profiles of a new series of designer cathinones.
Neuropharmacology. 2014 Apr;79:152-60. doi: 10.1016/j.neuropharm.2013.11.008. Epub 2013 Nov 22.
9
10
Locomotor stimulant and discriminative stimulus effects of 'bath salt' cathinones.
Behav Pharmacol. 2013 Sep;24(5-6):437-47. doi: 10.1097/FBP.0b013e328364166d.

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