Naidu P S, Kulkarni S K
Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India.
Methods Find Exp Clin Pharmacol. 2004 Jun;26(5):323-6. doi: 10.1358/mf.2004.26.5.831321.
Neuroleptics are extensively used in the treatment of schizophrenia and other affective disorders. Unfortunately their use is often associated with distressing side effects involving the extrapyramidal tract, such as Parkinsonism and tardive dyskinesia. Neuroleptic-induced catalepsy has long been used as a model for extrapyramidal side effects such as Parkinsonian-like bradykinesia associated with antipsychotic use in humans. In the present study, haloperidol (2 mg/kg i.p.) was administered to mice to induce catalepsy and cataleptic response was measured for the next 4 h at 1 h intervals. Haloperidol treatment in mice induced a strong cataleptic state within 1 h of injection, reaching a maximal plateau after 2 h and lasting for 4 h. Vehicle-treated animals did not display catalepsy as they remained less than 5 sec on the bar at each time point. Pretreatment with quercetin dose-dependently (25-100 mg/kg p.o.) reduced the catalepsy score in haloperidol-treated animals. A dose response study of quercetin showed a characteristic U-shaped response curve, with maximum suppression observed at a dose of 100 mg/kg. On increasing the dose of quercetin to 300 mg/kg, no statistically significant difference in catalepsy score was observed compared with the haloperidol-treated group. In conclusion, the findings of the present study strongly suggest that quercetin can be screened as a potential drug candidate or as an adjuvant for the treatment of neuroleptic-induced extrapyramidal side effects.
抗精神病药物被广泛用于治疗精神分裂症和其他情感障碍。不幸的是,它们的使用常常伴随着涉及锥体外系的令人苦恼的副作用,如帕金森症和迟发性运动障碍。抗精神病药物诱发的僵住症长期以来一直被用作锥体外系副作用的模型,例如与人类使用抗精神病药物相关的帕金森样运动迟缓。在本研究中,给小鼠腹腔注射氟哌啶醇(2毫克/千克)以诱发僵住症,并在接下来的4小时内每隔1小时测量僵住症反应。氟哌啶醇处理的小鼠在注射后1小时内诱导出强烈的僵住状态,2小时后达到最大平台期并持续4小时。用赋形剂处理的动物没有表现出僵住症,因为它们在每个时间点在杆上停留的时间少于5秒。槲皮素(25 - 100毫克/千克,口服)预处理剂量依赖性地降低了氟哌啶醇处理动物的僵住症评分。槲皮素的剂量反应研究显示出特征性 的U形反应曲线,在100毫克/千克的剂量下观察到最大抑制作用。将槲皮素的剂量增加到300毫克/千克时,与氟哌啶醇处理组相比,僵住症评分没有观察到统计学上的显著差异。总之,本研究结果强烈表明,槲皮素可以作为一种潜在的药物候选物或作为治疗抗精神病药物诱发的锥体外系副作用的佐剂进行筛选。