The risky cocktail: what combination effects can we expect between ecstasy and other amphetamines?

• Tipo: Artigo em Revista Científica Internacional
• Data: 2013

Autores

Diana Dias da Silva (Autor) Outra; Helena Carmo (Autor) FFUP; Elisabete Silva (Autor) Outra

Revista

Título: Archives of Toxicology

Vol. 87

Páginas: 111-122

ISSN: 0340-5761

Editora: Springer Nature

Indexação

ISI Web of Knowledge - 12 Citações

ISI Web of Science

Scopus - 16 Citações

Pubmed / Medline

Classificação Científica

FOS: Ciências médicas e da saúde > Medicina básica

CORDIS: Ciências da Saúde > Ciências farmacológicas > Toxicologia

Outras Informações

ID Authenticus: P-002-20V

DOI: 10.1007/s00204-012-0929-9

Abstract (EN): The recreational and illicit use of amphetaminic designer compounds, specially 3,4-methylenedioxymethamphetamine (MDMA; Ecstasy), is of concern worldwide. Such psychostimulating drugs are frequently present as complex mixtures in 'rave' pills, making concomitant polysubstance use a common trend. However, the understanding of possible combination effects with these substances is still scarce. The present study was aimed at predicting the cytotoxic effects of mixtures of four amphetaminic derivatives: MDMA, methamphetamine, 4-methylthioamphetamine and d-amphetamine in a human hepatoma cell line. Concentration-response curves for all single-mixture components were recorded by the MTT assay. Data obtained for individual agents were then used to compute the additivity expectations for mixtures of definite composition, using the pharmacological models of concentration addition (CA) and independent action. By comparing the predicted calculations with the experimentally observed effects, we concluded that CA accurately predicts the combination of amphetamines, which act together to generate additive effects over a large range of concentrations. Notably, we observed substantial mixture effects even when each drug was present at low concentrations, which individually produced unnoticeable effects. Nonetheless, for all tested mixtures, a small deviation from additivity was observed towards higher concentrations, particularly at high effect levels. A possible metabolic interaction, which could explain such deviation, was investigated, and it was observed that at higher mixture concentrations increased MDMA metabolism could be contributing to divergences from additivity. In conclusion, the present work clearly demonstrates that potentially harmful interactions among amphetaminic drugs are expected when these drugs are taken concomitantly.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 12