Matsumoto T, Maeno Y, Kato H, Seko-Nakamura Y, Monma-Ohtaki J, Ishiba A, Nagao M, Aoki Y
Criminal Investigation Laboratory, Aichi Prefectural Police H.Q., Sannomaru 2-chome 1-1, Naka-ku, Nagoya 460-8502, Japan; Department of Forensic Medicine, Nagoya City University Graduate School of Medical Sciences, Kawasumi 1, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
Department of Forensic Medicine, Nagoya City University Graduate School of Medical Sciences, Kawasumi 1, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
Eur Neuropsychopharmacol. 2014 Aug;24(8):1362-70. doi: 10.1016/j.euroneuro.2014.04.009. Epub 2014 May 10.
Using in vivo microdialysis, a comparative study was conducted to examine the effects of amphetamine-related compounds (methamphetamine, MAP; 3,4-methylenedioxymethamphetamine, MDMA; p-methoxyamphetamine, PMA; p-methoxymethamphetamine, PMMA; 4-methylthioamphetamine, 4-MTA; 3,4,5-trimethoxyamphetamine, TMA; 2,5-dimethoxy-4-iodoamphetamine, DOI) on extracellular levels of serotonin (5-HT) and dopamine (DA). Dialysates were assayed using HPLC equipped with electrochemical detector following i.p. administration with each drug at a dose of 5 mg/kg. MAP was found to drastically and rapidly increase 5-HT and DA levels (870% and 1460%, respectively). PMA, PMMA, and 4-MTA slightly increased DA levels (150-290%) but remarkably increased 5-HT levels (540-900%). In contrast, TMA and DOI caused no detectable changes in levels of both monoamines. We observed that the potent DA-releasing action of MAP was remarkably decreased by introduction of methoxy or methylthio group at the para position (MAP vs. PMMA or 4-MTA), but introduction of two additional adjacent methoxy groups into PMA totally abolished its 5-HT-/DA-releasing action (PMA vs. TMA). In addition, para-mono-substituted compounds inhibited both monoamine oxidase (MAO) enzymes more strongly than other compounds; PMA and 4-MTA exhibited submicromolar IC50 values for MAO-A. On the other hand, TMA scarcely affected the activity of both MAO enzymes as well as extracellular levels of 5-HT and DA. In this comparative study, MDMA, PMA, and 4-MTA functioned similar to PMMA, a typical empathogen; these findings therefore could be helpful in clarifying the psychopharmacological properties of amphetamine-related, empathogenic designer drugs.
利用体内微透析技术，进行了一项比较研究，以考察苯丙胺相关化合物（甲基苯丙胺、MAP；3,4-亚甲基二氧基甲基苯丙胺、MDMA；对甲氧基苯丙胺、PMA；对甲氧基甲基苯丙胺、PMMA；4-甲硫基苯丙胺、4-MTA；3,4,5-三甲氧基苯丙胺、TMA；2,5-二甲氧基-4-碘苯丙胺、DOI）对细胞外5-羟色胺（5-HT）和多巴胺（DA）水平的影响。腹腔注射每种药物剂量为5mg/kg后，使用配备电化学检测器的高效液相色谱法对透析液进行检测。发现MAP能急剧且迅速地升高5-HT和DA水平（分别升高870%和1460%）。PMA、PMMA和4-MTA使DA水平略有升高（150%-290%），但使5-HT水平显著升高（540%-900%）。相反，TMA和DOI未引起两种单胺水平的可检测变化。我们观察到，在对位引入甲氧基或甲硫基会显著降低MAP的强效DA释放作用（MAP与PMMA或4-MTA相比），但在PMA中再引入两个相邻甲氧基则完全消除了其5-HT/DA释放作用（PMA与TMA相比）。此外，对位单取代化合物比其他化合物更强烈地抑制两种单胺氧化酶（MAO）；PMA和4-MTA对MAO-A表现出亚微摩尔IC50值。另一方面，TMA几乎不影响两种MAO酶的活性以及细胞外5-HT和DA水平。在这项比较研究中，MDMA、PMA和4-MTA的作用与典型的致共情剂PMMA相似；因此，这些发现可能有助于阐明苯丙胺相关致共情设计药物的精神药理学特性。
