Therapeutic effects of methimazole on 3,4-methylenedioxymethamphetamine-induced hyperthermia and serotonergic neurotoxicity.

Methimazole (MMI), a drug that inhibits thyroid hormone synthesis, alleviates several harmful effects of MDMA (ecstasy) in male rats. MMI reduced MDMA-induced hyperthermia (overheating) and increased heat loss through peripheral vasodilation. PET scans showed that MDMA raised glucose uptake in skeletal muscles, which MMI pretreatment prevented. Immunohistochemistry revealed that MMI lessened the loss of serotonin transporter fibers, a sign of neurotoxicity caused by MDMA. In the forced swimming test, rats given MMI swam longer and were immobile less, indicating more active behavior. The findings suggest MMI lowers body temperature, reduces neurotoxicity, and promotes excited behavior, though further research is needed for clinical use.

Study at a glance

Abstract

3,4-methylenedioxymethamphetamine (MDMA) is a popular recreational drug, however over 200 studies demonstrate that acute (e.g. hyperthermia, rhabdomyolysis) and chronic (e.g. neurotoxicity) toxicity effects of MDMA were observed in different animals. Methimazole (MMI), an inhibitor of thyroid hormone synthesis, was found to significantly reduce the HSP72 expression of heat stress induced in fibroblasts. Hence, we attempted to understand the effects of MMI on MDMA induced changes in vivo. Male SD rats were randomly divided into four groups as follows:(a) water-saline (b) water-MDMA (c) MMI-saline and (d) MMI-MDMA group. In the temperature analysis test, MMI was found to alleviate MDMA-induced hyperthermia and increase the heat loss index (HLI), revealing its peripheral vasodilation effect. PET experiment suggested that MDMA induced elevated glucose uptake by skeletal muscles, which was resolved by MMI pretreatment. IHC staining (serotonin transporter, SERT) showed the evidence of neurotoxicity caused by MDMA (serotonin fiber loss), which was alleviated by MMI. Furthermore, the animal behaviour test (forced swimming test, FST) showed higher swimming time but lower immobility time in MMI-MDMA and MMI-saline groups. Taken together, treatment of MMI shows benefits such as lowered body temperature, alleviation of neurotoxicity and excited behaviour. However, further investigations should be conducted in the future to provide in-depth evidence for its clinical use.