Studies on the mechanisms underlying amiloride enhancement of 3,4-methylenedioxymethamphetamine-induced serotonin depletion in rats.
European journal of pharmacology May 21, 2007 Beatriz Goñi-allo, Elena Puerta, Isabel Hervias et al. 13 citations
Amiloride, a drug that blocks sodium/calcium and sodium/hydrogen exchange, worsens long-term serotonin loss caused by MDMA in rats. Unlike with methamphetamine, amiloride also increases MDMA-induced hyperthermia. The antidepressant fluoxetine fully protects against serotonin depletion without affecting hyperthermia, while calcium channel blockers do not. The effect appears mediated by sodium/hydrogen exchange blockade, as dimethylamiloride produces similar results. When rats are kept at 15°C, hyperthermia does not develop and serotonin levels remain normal after seven days. These findings suggest that amiloride's enhancement of serotonin loss depends on its ability to amplify MDMA-induced hyperthermia, and that blocking sodium/hydrogen exchange may combine with hyperthermia to make serotonin nerve endings more vulnerable.