Synthesis and in vitro toxicity of 4-MTA, its characteristic clandestine synthesis byproducts and related sulfur substituted alpha-alkylthioamphetamines.
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.
Cloonan
Suzanne M
SM
School of Biochemistry and Immunology, Trinity College Dublin, Ireland.
Keating
John J
JJ
Corrigan
Desmond
D
O'Brien
John E
JE
Kavanagh
Pierce V
PV
Williams
D Clive
DC
Meegan
Mary J
MJ
D000662:Amphetamines / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity*; D002460:Cell Line; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D006801:Humans; D008694:Methamphetamine; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D010627:Phenethylamines; D013455:Sulfur
D000662:Amphetamines; D010627:Phenethylamines; D008694:Methamphetamine; C078956:4-methylthioamphetamine; D013455:Sulfur