Synthesis and in vitro toxicity of 4-MTA, its characteristic clandestine synthesis byproducts and related sulfur substituted alpha-alkylthioamphetamines.

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Cloonan SM, Keating JJ, Corrigan D, O'Brien JE, Kavanagh PV, Williams DC, Meegan MJ

Synthesis and in vitro toxicity of 4-MTA, its characteristic clandestine synthesis byproducts and related sulfur substituted alpha-alkylthioamphetamines.

Bioorg Med Chem. 2010 Jun 1;18(11):4009-31. doi: 10.1016/j.bmc.2010.04.022. Epub 2010 Apr 13.

PubMed ID
20466553 [ View in PubMed
]
Abstract

4-Methylthioamphetamine (4-MTA) is recognised as a 3,4-methylenedioxymethamphetamine (MDMA)-like drug of abuse. Such amphetamine-type drugs often contain byproducts of uncontrolled, illegal clandestine synthetic processes. We report the isolation and structural identification of a number of novel pyridines, dihydropyridone and N,N-di(1-aryl-2-propyl) amines as route-specific byproducts associated with clandestine synthesis of 4-MTA and related amphetamines. We report the in vitro cytotoxicity of 4-MTA, its synthesis byproducts together with some structurally related sulfur substituted alpha-alkyl phenethylamines in cell lines overexpressing human monoamine transporters as well as in a primary neuronal cell line model and a dopaminergic neuroblastoma cell line. 4-MTA along with a number of other structurally related amphetamine derivatives and synthetic impurities were found to be cytotoxic to these cells within pharmacologically defined concentrations implying that 4-MTA is a cytotoxic agent in vitro and therefore might have the potential to be a neurotoxic agent in vivo.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
MidomafetamineSodium-dependent dopamine transporterIC 50 (nM)1442N/AN/ADetails
MidomafetamineSodium-dependent noradrenaline transporterIC 50 (nM)405N/AN/ADetails
MidomafetamineSodium-dependent serotonin transporterIC 50 (nM)425N/AN/ADetails