Bishnoi Mahendra, Boparai Ravneet K
Department of Pharmacology, Southern Illinois University School of Medicine, Springfield, IL, USA.
Methods Mol Biol. 2012;829:193-201. doi: 10.1007/978-1-61779-458-2_12.
Long-term treatment with haloperidol is associated with a number of extrapyramidal side effects. This limitation presents a marked therapeutic challenge. The present method (21 days administration of haloperidol, 5 mg/kg, i.p.) has been established to gain deeper insight into the molecular etiology (inflammation and apoptosis) of haloperidol-induced cellular death. In the present model, besides the corresponding increase in the vacuous chewing movements (VCMs), enhanced oxidative stress, there was a significant increase in cellular markers of inflammation and apoptotic protein (caspase-3), leading to cellular death. We also suggest that this model will be effective in preclinical testing of new chemical entities for the treatment of haloperidol induced tardive dyskinesia and related symptoms.
长期使用氟哌啶醇治疗会引发多种锥体外系副作用。这一局限性带来了显著的治疗挑战。目前已建立了本方法（腹腔注射5 mg/kg氟哌啶醇，持续给药21天），以更深入地了解氟哌啶醇诱导细胞死亡的分子病因（炎症和凋亡）。在当前模型中，除了空嚼运动（VCMs）相应增加、氧化应激增强外，炎症细胞标志物和凋亡蛋白（半胱天冬酶-3）也显著增加，导致细胞死亡。我们还认为，该模型将有效地用于治疗氟哌啶醇诱导的迟发性运动障碍及相关症状的新化学实体的临床前测试。
