3,4-Methylenedioxypyrovalerone prevents while methylone enhances methamphetamine-induced damage to dopamine nerve endings: β-ketoamphetamine modulation of neurotoxicity by the dopamine transporter.
3,4-Methylenedioxypyrovalerone prevents while methylone enhances methamphetamine-induced damage to dopamine nerve endings: β-ketoamphetamine modulation of neurotoxicity by the dopamine transporter.
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DOI：
10.1111/jnc.13048
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发表时间：
2015-04
影响因子：
4.7
通讯作者：
Kuhn DM
中科院分区：
文献类型：
--
作者：
Anneken JH;Angoa-Pérez M;Kuhn DM
甲基酮、3，4-亚甲基二氧基吡喃丙酮(MDPV)和甲氧基苯丙酮是“浴盐”的精神活性成分，它们的滥用代表着越来越多的公共卫生保健关注。这些药物是卡西酮的衍生物，在化学上被归类为β-酮基苯丙胺。由于它们在结构上与苯丙胺非常相似，所以甲基酮、MDPV和甲氧麻黄酮具有大部分的药理、神经化学和行为特性。他们行动中的一个分歧点是对中枢神经系统造成损害的能力。与甲基苯丙胺不同，β-酮基苯丙胺不会损害多巴胺(DA)神经末梢。然而，甲氧麻黄酮已被证明显著加重了甲基苯丙胺的神经毒性。浴盐配方含有许多不同的精神活性成分，滥用浴盐的人也共同滥用其他非法药物。因此，我们评估了甲酮、MDPV、甲氧麻黄酮和甲基苯丙胺对DA神经末梢的影响。β-酮基苯丙胺单独或在所有可能的两种药物组合中不会对DA神经末梢造成损害，但确实会导致体温过高。MDPV完全防止甲基苯丙胺的神经毒性作用，而甲基酮则使其加重。MDPV和甲基酮都不能减弱甲基苯丙胺的高热效应。MDPV的强大神经保护作用延伸到苯丙胺、3，4-亚甲基二氧基甲基苯丙胺和MPTP诱导的神经毒性。这些结果表明，β-酮苯丙胺类药物是DA转运体的非底物阻滞剂(即MDPV)，可防止甲基苯丙胺的神经毒性，而那些作为DA转运体摄取底物并导致DA释放的药物(如甲酮、甲氧麻黄酮)则加重神经毒性。
Methylone, 3,4-methylenedioxypyrovalerone (MDPV), and mephedrone are psychoactive ingredients of ‘bath salts’ and their abuse represents a growing public health care concern. These drugs are cathinone derivatives and are classified chemically as β-ketoamphetamines. Because of their close structural similarity to the amphetamines, methylone, MDPV, and mephedrone share most of their pharmacological, neurochemical, and behavioral properties. One point of divergence in their actions is the ability to cause damage to the CNS. Unlike methamphetamine, the β-ketoamphetamines do not damage dopamine (DA) nerve endings. However, mephedrone has been shown to significantly accentuate methamphetamine neurotoxicity. Bath salt formulations contain numerous different psychoactive ingredients, and individuals who abuse bath salts also coabuse other illicit drugs. Therefore, we have evaluated the effects of methylone, MDPV, mephedrone, and methamphetamine on DA nerve endings. The β-ketoamphetamines alone or in all possible two-drug combinations do not result in damage to DA nerve endings but do cause hyperthermia. MDPV completely protects against the neurotoxic effects of methamphetamine while methylone accentuates it. Neither MDPV nor methylone attenuates the hyperthermic effects of methamphetamine. The potent neuroprotective effects of MDPV extend to amphetamine-, 3,4-methylenedioxymethamphetamine-, and MPTP-induced neurotoxicity. These results indicate that β-ketoamphetamine drugs that are non-substrate blockers of the DA transporter (i.e., MDPV) protect against methamphetamine neurotoxicity, whereas those that are substrates for uptake by the DA transporter and which cause DA release (i.e., methylone, mephedrone) accentuate neurotoxicity.