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美西律对脊髓损伤大鼠抗痛觉过敏作用缺乏立体选择性。

Lack of stereoselectivity for the antiallodynic effect of mexiletine in spinally injured rats.

作者信息

Wu W P, Nordmark J, Wiesenfeld-Hallin Z, Xu X J

机构信息

Department of Medical Laboratory Sciences and Technology, Division of Clinical Neurophysiology, Karolinska Institutet, Huddinge University Hospital, Huddinge, Sweden.

出版信息

Eur J Pain. 2000;4(4):409-12. doi: 10.1053/eujp.2000.0201.

Abstract

Systemically administered mexiletine, an antiarrhythmic, has been shown to also possess analgesic properties in some conditions of neuropathic pain. It has been suggested that the analgesic effect of mexiletine may be derived from the action of one of its optical isomers, (+)(S)-mexiletine. In the present study, we have compared the effects of systemic (-)-(R)- and (+)-(S)-mexiletine, on chronic mechanical allodynia-like behaviour in spinally injured rats, a model of central neuropathic pain in which racemic mexiletine has been shown to be active. I.p. racemic mexiletine as well as (-)-(R)- and (+)(S)-mexiletine at 25 mg/kg all produced significant, but brief, alleviation of mechanical allodynia in a similar fashion as assessed with von-Frey hair elicited vocalization in the spinally injured rats. A slight increase in motor impairment was observed in all three groups which reached statistical significance for the racemic mexiletine and (+)-(S)-mexiletine. Our results suggest that both isomers of mexiletine contribute to the antiallodynic effect in this model of central pain.

摘要

全身性给予的抗心律失常药物美西律,已被证明在某些神经性疼痛情况下也具有镇痛特性。有人提出,美西律的镇痛作用可能源于其一种光学异构体(+)(S)-美西律的作用。在本研究中,我们比较了全身性给予(-)-(R)-美西律和(+)-(S)-美西律对脊髓损伤大鼠慢性机械性异常性疼痛样行为的影响,脊髓损伤大鼠是中枢神经性疼痛的一种模型,已证明消旋美西律在该模型中具有活性。腹腔注射25mg/kg的消旋美西律以及(-)-(R)-美西律和(+)(S)-美西律,均以与用von-Frey毛发诱发脊髓损伤大鼠发声评估的类似方式,产生了显著但短暂的机械性异常性疼痛缓解。在所有三组中均观察到运动功能障碍略有增加,消旋美西律和(+)-(S)-美西律组达到统计学显著性。我们的结果表明,美西律的两种异构体均对该中枢性疼痛模型中的抗异常性疼痛作用有贡献。

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