p-Methylthioamphetamine is a potent new non-neurotoxic serotonin-releasing agent

Xuemei Huang, Danuta Marona-Lewicka, David E. Nichols

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Abstract

p-Methylthioamphetamine (MTA), was compared to p-chloroamphetamine (PCA) in a number of pharmacological assays. MTA was about 2-fold more potent than PCA at inhibiting synaptosomal uptake of [3H]5-hydroxytryptamine ([3H]5-HT), and about 7-fold and 10-fold less potent than PCA at inhibiting synaptosomal uptake of [3H]dopamine and [3H]norepinephrine, respectively. In drug discrimination assays, MTA was nearly equipotent to PCA in animals trained to discriminate saline from 3,4-methylenedioxymethamphetamine (MDMA), or two related analogues S-(+)-N-methyl-1-(1,3-benzodioxol-5-yl)-2-butanamine (S-MBDB) or 5-methoxy-6-methyl-2-aminoindan (MMAI). MTA caused dose-dependent increases of tritium efflux from superfused rat frontal cortex slices preloaded with [3H]5-HT, comparable to that induced by an equal molar concentration of PCA. The potential neurotoxicity of MTA was examined by measuring monoamine and metabolite levels at one week following an acute dose. A 10 mg/kg dose of PCA caused a 70-90% decrease of cortical, hippocampal and striatal 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) levels, while twice the molar dose of MTA (21.3 mg/kg) had no effect. Thus, MTA is a potent, selective, serotonin releaser, apparently devoid of serotonin neurotoxic effects. This work also supports the idea that catecholamine systems may play a critical role in the neurotoxicity of PCA-like compounds.

Original languageEnglish (US)
Pages (from-to)31-38
Number of pages8
JournalEuropean Journal of Pharmacology
Volume229
Issue number1
DOIs
StatePublished - Dec 8 1992

Fingerprint

p-Chloroamphetamine
Serotonin Agents
Serotonin
Corpus Striatum
N-Methyl-3,4-methylenedioxyamphetamine
Hydroxyindoleacetic Acid
Tritium
Frontal Lobe
4-methylthioamphetamine
Catecholamines
Dopamine
Norepinephrine
Pharmacology

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Huang, Xuemei ; Marona-Lewicka, Danuta ; Nichols, David E. / p-Methylthioamphetamine is a potent new non-neurotoxic serotonin-releasing agent. In: European Journal of Pharmacology. 1992 ; Vol. 229, No. 1. pp. 31-38.
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abstract = "p-Methylthioamphetamine (MTA), was compared to p-chloroamphetamine (PCA) in a number of pharmacological assays. MTA was about 2-fold more potent than PCA at inhibiting synaptosomal uptake of [3H]5-hydroxytryptamine ([3H]5-HT), and about 7-fold and 10-fold less potent than PCA at inhibiting synaptosomal uptake of [3H]dopamine and [3H]norepinephrine, respectively. In drug discrimination assays, MTA was nearly equipotent to PCA in animals trained to discriminate saline from 3,4-methylenedioxymethamphetamine (MDMA), or two related analogues S-(+)-N-methyl-1-(1,3-benzodioxol-5-yl)-2-butanamine (S-MBDB) or 5-methoxy-6-methyl-2-aminoindan (MMAI). MTA caused dose-dependent increases of tritium efflux from superfused rat frontal cortex slices preloaded with [3H]5-HT, comparable to that induced by an equal molar concentration of PCA. The potential neurotoxicity of MTA was examined by measuring monoamine and metabolite levels at one week following an acute dose. A 10 mg/kg dose of PCA caused a 70-90{\%} decrease of cortical, hippocampal and striatal 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) levels, while twice the molar dose of MTA (21.3 mg/kg) had no effect. Thus, MTA is a potent, selective, serotonin releaser, apparently devoid of serotonin neurotoxic effects. This work also supports the idea that catecholamine systems may play a critical role in the neurotoxicity of PCA-like compounds.",
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p-Methylthioamphetamine is a potent new non-neurotoxic serotonin-releasing agent. / Huang, Xuemei; Marona-Lewicka, Danuta; Nichols, David E.

In: European Journal of Pharmacology, Vol. 229, No. 1, 08.12.1992, p. 31-38.

Research output: Contribution to journalArticle

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