The effects of MDMA and metabolites were investigated in cultured rat and human renal cells, with human cells acquired from nephrectomies. The researchers studied the following compounds; MDMA, MDA, alpha-methyl-dopamine (Alpha-MeDA), 5-glutathion-S-yl-N-methyl-AlphaMeDA, 5-glutathion-S-yl-Alpha-MeDA, and 2,5-bis(glutathion-S-yl)-alphaMeDA. Cells were incubated for 24 h with one of these compounds, at concentrations of 100, 200, 400 or 800 mcM. In some studies, cells were pretreated with 250 mcM of the Gamma-GT inhibitor acivicin or 10 mcM of the aminopeptidase M inhibitor bestatin for 20 min. Cell viability was measured with the dye MTT. All concentrations of MDMA and MDA failed to produce cytotoxicity in human or rat kidney cells. However, exposure to the highest concentration of Alpha-MeDA produced significant decreases in human and rat kidney cell viability. GSH conjugates of Alpha-MeDA (the glutathion compounds) produced even greater decreases in kidney cell viability. Rat kidney cells were less sensitive to 2,5-bis(glutathion-S-yl)-AlphaMeDA than to 5-glutathion-S-yl-alphaMeDA, whereas human kidney cells were equally sensitive to both compounds. Acivicin and bestatin treatment potentiated the induction of cell death after 5-glutathion-S-yl-AlphaMeDA, but it did not potentiate the effects of the 2,5-bis compound. The authors seem to be unaware of the fact that HMMA and HMA, and not MDA, are major metabolites in humans, as they failed to study the effects of either of these compounds. Concentrations used in these studies are far higher than expected to occur in humans. So far, there have not been any investigations into possible kidney damage with neurotoxic MDMA regimens in rats. This suggests that possible nephrotoxicity after MDMA, if it exists in vivo, does not occur through the same processes that cause neurotoxicity.