RESUMO
3,4-methylenedioxy-methamphetamine is taken recreationally by thousands of people, especially the young, across the globe. It is highly associated with electronic music and its use in the UK remains high at around 4.5% of 16-24 year olds. This review discusses both the short- and long-term effects of 3,4-methylenedioxy-methamphetamine including methods by which some of these adverse effects can be prevented or even reversed to increase the safety of the commonly used drug.
Assuntos
N-Metil-3,4-Metilenodioxianfetamina/efeitos adversos , N-Metil-3,4-Metilenodioxianfetamina/farmacocinética , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/fisiopatologia , Humanos , Drogas Ilícitas/efeitos adversos , Drogas Ilícitas/farmacocinética , N-Metil-3,4-Metilenodioxianfetamina/uso terapêuticoRESUMO
Phagocytes destroy ingested microbes by producing hypochlorous acid (HOCl) from chloride ions (Cl-) and hydrogen peroxide within phagolysosomes, using the enzyme myeloperoxidase. HOCl, the active ingredient in bleach, has antibacterial/antiviral properties. As myeloperoxidase is needed for HOCl production, non-myeloid cells are considered incapable of producing HOCl. Here, we show that epithelial, fibroblast and hepatic cells have enhanced antiviral activity in the presence of increasing concentrations of sodium chloride (NaCl). Replication of enveloped/non-enveloped, DNA (herpes simplex virus-1, murine gammaherpesvirus 68) and RNA (respiratory syncytial virus, influenza A virus, human coronavirus 229E, coxsackievirus B3) viruses are inhibited in a dose-dependent manner. Whilst treatment with sodium channel inhibitors did not prevent NaCl-mediated virus inhibition, a chloride channel inhibitor reversed inhibition by NaCl, suggesting intracellular chloride is required for antiviral activity. Inhibition is also reversed in the presence of 4-aminobenzoic hydrazide, a myeloperoxidase inhibitor, suggesting epithelial cells have a peroxidase to convert Cl- to HOCl. A significant increase in intracellular HOCl production is seen early in infection. These data suggest that non-myeloid cells possess an innate antiviral mechanism dependent on the availability of Cl- to produce HOCl. Antiviral activity against a broad range of viral infections can be augmented by increasing availability of NaCl.