Therapeutic effects of methimazole on 3,4-methylenedioxymethamphetamine-induced hyperthermia and serotonergic neurotoxicity.
I-Hsun Li, Tsung-ta Liu, Ying-chen Chen, Sheng-huang Hsiao, Hao-yuan Hung, Li-yun Fann, Jui-hu Shih
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie August 1, 2023 Peer reviewed DOI: 10.1016/j.biopha.2023.114880 via PubMed
Summary
Methimazole (MMI) was found to alleviate the hyperthermia and neurotoxicity induced by MDMA in male SD rats. MMI treatment increased the heat loss index and resolved elevated glucose uptake in skeletal muscles caused by MDMA. Behavioral tests showed that rats treated with MMI had higher swimming times and lower immobility times, indicating improved activity. These findings suggest potential benefits of MMI for mitigating MDMA's harmful effects, although further research is needed.
Study at a glance
| Design | randomized controlled trial |
|---|---|
| Population | male SD rats |
| Key finding | MMI alleviated MDMA-induced hyperthermia and neurotoxicity in male SD rats. |
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.