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 DOI: 10.1016/j.biopha.2023.114880 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Controlled experiment Peer reviewed |
|---|---|
| Population | Male Sprague-Dawley rats |
| Interventions | Methimazole MDMA |
| Topics | MDMA Serotonin |
| Keywords | Forced swimming test Hyperthermia Methimazole PET Serotonergic neurotoxicity |
| Key findings | Methimazole alleviates MDMA-induced hyperthermia, reduces serotonergic neurotoxicity, and increases active behavior in 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.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
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and 12 more in the library