Acetaminophen improves tardive akathisia induced by dopamine D2 receptor antagonists
Acetaminophen improves tardive akathisia induced by dopamine D2 receptor antagonists
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DOI：
10.1016/j.jphs.2022.10.006
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发表时间：
2022-11-09
影响因子：
3.5
通讯作者：
Kaneko，Shuji
中科院分区：
文献类型：
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作者：
Nagaoka，Koki;Nagayasu，Kazuki;Kaneko，Shuji
迟发性静坐症是一种运动障碍，其特征是内部不安，无法控制的运动冲动，导致重复运动。这是长期使用多巴胺D₂受体拮抗剂治疗的常见副作用。在本研究中，我们分析了FDA不良事件报告系统和IBM MarketScan研究数据库，以找到一种可以与多巴胺D₂受体拮抗剂联合使用的药物，并且仍然可以降低静坐症的风险。对乙酰氨基酚被认为是最有效的抑制静坐症的药物。在一项验证该假说的实验中，长期使用氟哌啶醇治疗大鼠可引起静坐症症状，包括刻板行为和运动活动增加，以及静止时间减少。对乙酰氨基酚急性治疗可显著减轻氟哌啶醇引起的静坐症。在这些大鼠的腹侧纹状体中，对乙酰氨基酚阻止了氟哌啶醇诱导的c-Fos +前脑啡肽+神经元数量的减少。这些结果表明，对乙酰氨基酚通过激活间接通路中棘神经元有效地抑制迟发性无运动障碍。
Tardive akathisia is a movement disorder characterized by internal restlessness with an uncontrollable urge to move, leading to repetitive movements. It is a common side effect of long-term treatment with dopamine D₂ receptor antagonists. In the present study, we analyzed the FDA Adverse Event Reporting System and IBM MarketScan Research Database to find a drug that can be used concomitantly with dopamine D₂ receptor antagonists and still reduce the risk of akathisia. Acetaminophen was determined to be the most effective akathisia-suppressing drug. In an experimental validation of the hypothesis, chronic treatment of rats with haloperidol caused akathisia symptoms, including increased stereotyped behavior and locomotor activity, and decreased immobility time. Acute treatment with acetaminophen significantly attenuated haloperidol-induced akathisia. In the ventral striata of these rats, acetaminophen prevented haloperidol-induced decrease in the number of c-Fos⁺ preproenkephalin⁺ neurons. These results suggest that acetaminophen is effective in suppressing tardive akathisia by activating indirect-pathway medium spiny neurons.