title: 5-hydroxytryptamine- and dopamine-releasing effects of ring-substituted amphetamines on rat brain: a comparative study using in vivo microdialysis.
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.
authors.affiliation: 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.
authors.forename: T
authors.initials: T
authors.lastname: Matsumoto
authors.affiliation: Department of Forensic Medicine, Nagoya City University Graduate School of Medical Sciences, Kawasumi 1, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Maeno
authors.affiliation: Department of Forensic Medicine, Nagoya City University Graduate School of Medical Sciences, Kawasumi 1, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Kato
authors.affiliation: Department of Forensic Medicine, Nagoya City University Graduate School of Medical Sciences, Kawasumi 1, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Seko-Nakamura
authors.affiliation: Department of Forensic Medicine, Nagoya City University Graduate School of Medical Sciences, Kawasumi 1, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Monma-Ohtaki
authors.affiliation: Criminal Investigation Laboratory, Aichi Prefectural Police H.Q., Sannomaru 2-chome 1-1, Naka-ku, Nagoya 460-8502, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Ishiba
authors.affiliation: Department of Forensic Medicine, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-0037, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Nagao
authors.affiliation: Department of Forensic Medicine, Nagoya City University Graduate School of Medical Sciences, Kawasumi 1, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Aoki
mesh_terms: D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D004298:Dopamine / Q000378:metabolism*; D045604:Extracellular Fluid / Q000187:drug effects / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D008297:Male; D017551:Microdialysis; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism*; D013997:Time Factors
chemical_list: D000662:Amphetamines; D000697:Central Nervous System Stimulants; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; C078956:4-methylthioamphetamine; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D004298:Dopamine
keywords: 5-hydroxytryptamine; Amphetamines; Dopamine; Microdialysis; Monoamine oxidase