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5-hydroxytryptamine- and dopamine-releasing effects of ring-substituted amphetamines on rat brain: a comparative study using in vivo microdialysis.
Eur Neuropsychopharmacol. 2014 Aug; 24(8):1362-70.EN

Abstract

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.

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Authors+Show Affiliations

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. Electronic address: apkasouken@yahoo.co.jp.

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.

Seko-Nakamura Y

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.

Criminal Investigation Laboratory, Aichi Prefectural Police H.Q., Sannomaru 2-chome 1-1, Naka-ku, Nagoya 460-8502, Japan.

Department of Forensic Medicine, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-0037, Japan.

Department of Forensic Medicine, Nagoya City University Graduate School of Medical Sciences, Kawasumi 1, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.

MeSH

AmphetaminesAnimalsBrainCentral Nervous System StimulantsChromatography, High Pressure LiquidDopamineExtracellular FluidHydroxyindoleacetic AcidInhibitory Concentration 50MaleMicrodialysisN-Methyl-3,4-methylenedioxyamphetamineRatsRats, WistarSerotoninTime Factors

Pub Type(s)

Comparative Study

Journal Article

Language

eng

PubMed ID

24862256

Citation

Matsumoto, T, et al. "5-hydroxytryptamine- and Dopamine-releasing Effects of Ring-substituted Amphetamines On Rat Brain: a Comparative Study Using in Vivo Microdialysis." European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology, vol. 24, no. 8, 2014, pp. 1362-70.

Matsumoto T, Maeno Y, Kato H, et al. 5-hydroxytryptamine- and dopamine-releasing effects of ring-substituted amphetamines on rat brain: a comparative study using in vivo microdialysis. Eur Neuropsychopharmacol. 2014;24(8):1362-70.

Matsumoto, T., Maeno, Y., Kato, H., Seko-Nakamura, Y., Monma-Ohtaki, J., Ishiba, A., Nagao, M., & Aoki, Y. (2014). 5-hydroxytryptamine- and dopamine-releasing effects of ring-substituted amphetamines on rat brain: a comparative study using in vivo microdialysis. European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology, 24(8), 1362-70. https://doi.org/10.1016/j.euroneuro.2014.04.009

Matsumoto T, et al. 5-hydroxytryptamine- and Dopamine-releasing Effects of Ring-substituted Amphetamines On Rat Brain: a Comparative Study Using in Vivo Microdialysis. Eur Neuropsychopharmacol. 2014;24(8):1362-70. PubMed PMID: 24862256.

* Article titles in AMA citation format should be in sentence-case

TY - JOUR T1 - 5-hydroxytryptamine- and dopamine-releasing effects of ring-substituted amphetamines on rat brain: a comparative study using in vivo microdialysis. AU - Matsumoto,T, AU - Maeno,Y, AU - Kato,H, AU - Seko-Nakamura,Y, AU - Monma-Ohtaki,J, AU - Ishiba,A, AU - Nagao,M, AU - Aoki,Y, Y1 - 2014/05/10/ PY - 2012/07/12/received PY - 2014/04/06/revised PY - 2014/04/27/accepted PY - 2014/5/28/entrez PY - 2014/5/28/pubmed PY - 2015/3/31/medline KW - 5-hydroxytryptamine KW - Amphetamines KW - Dopamine KW - Microdialysis KW - Monoamine oxidase SP - 1362 EP - 70 JF - European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology JO - Eur Neuropsychopharmacol VL - 24 IS - 8 N2 - 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. SN - 1873-7862 UR - https://www.unboundmedicine.com/medline/citation/24862256/5_hydroxytryptamine__and_dopamine_releasing_effects_of_ring_substituted_amphetamines_on_rat_brain:_a_comparative_study_using_in_vivo_microdialysis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0924-977X(14)00131-X DB - PRIME DP - Unbound Medicine ER -