Metabolites of the ring-substituted stimulants MDMA, methylone and MDPV differentially affect human monoaminergic systems.
J Psychopharmacol
; 33(7): 831-841, 2019 07.
Article
em En
| MEDLINE
| ID: mdl-31038382
ABSTRACT
BACKGROUND:
Amphetamine analogs with a 3,4-methylenedioxy ring-substitution are among the most popular illicit drugs of abuse, exerting stimulant and entactogenic effects. Enzymatic N-demethylation or opening of the 3,4-methylenedioxy ring via O-demethylenation gives rise to metabolites that may be pharmacologically active. Indeed, previous studies in rats show that specific metabolites of 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxymethcathinone (methylone) and 3,4-methylenedioxypyrovalerone (MDPV) can interact with monoaminergic systems.AIM:
Interactions of metabolites of MDMA, methylone and MDPV with human monoaminergic systems were assessed.METHODS:
The ability of parent drugs and their metabolites to inhibit uptake of tritiated norepinephrine, dopamine and serotonin (5-HT) was assessed in human embryonic kidney 293 cells transfected with human monoamine transporters. Binding affinities and functional activity at monoamine transporters and various receptor subtypes were also determined.RESULTS:
MDMA and methylone displayed greater potency to inhibit norepinephrine uptake as compared to their effects on dopamine and 5-HT uptake. N-demethylation of MDMA failed to alter uptake inhibition profiles, whereas N-demethylation of methylone decreased overall transporter inhibition potencies. O-demethylenation of MDMA, methylone and MDPV resulted in catechol metabolites that maintained norepinephrine and dopamine uptake inhibition potencies, but markedly reduced activity at 5-HT uptake. O-methylation of the catechol metabolites significantly decreased norepinephrine uptake inhibition, resulting in metabolites lacking significant stimulant properties.CONCLUSIONS:
Several metabolites of MDMA, methylone and MDPV interact with human transporters and receptors at pharmacologically relevant concentrations. In particular, N-demethylated metabolites of MDMA and methylone circulate in unconjugated form and could contribute to the in vivo activity of the parent compounds in human users.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pirrolidinas
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N-Metil-3,4-Metilenodioxianfetamina
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Benzodioxóis
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Estimulantes do Sistema Nervoso Central
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Metanfetamina
Limite:
Humans
Idioma:
En
Revista:
J Psychopharmacol
Ano de publicação:
2019
Tipo de documento:
Article