Shireen Erum, Naeem Sadaf, Inam Qurrat-ul-Aen, Haleem Darakhshan Jabeen
Department of Biochemistry, University of Karachi, Karachi, Pakistan.
Pak J Pharm Sci. 2013 Mar;26(2):271-6.
The present study was designed to monitor extrapyramidal symptoms (EPS) elicited by the oral administration of haloperidol at clinically recommended doses and to compare it with EPS produced when the drug is injected intraperitoneally at doses used in animal research. Rats injected with haloperidol at a dose of 1 mg/kg daily for 5 weeks exhibited akinesia in an open field and impaired motor coordination. Effects of the drug on motor coordination but not on open field akinesia were attenuated gradually from 2-5 weeks of treatment. Oral administration of haloperidol in drinking water at clinically recommended dose exhibited decreased exploratory activity without producing akinesia. Motor coordination was impaired maximally after 3 weeks and tolerance was developed in the drug induced motor impairment after 5 weeks of treatment. Intensity of vacuous chewing movements (VCMs) and tardive VCMs was greater by oral administration than intraperitoneal injections of haloperidol. The present results showed that oral administration of haloperidol expected to produce sustained effect may result in tolerance in acute parkinsonian like effects but more intensity of tardive dyskinesia. We suggest that drugs which may helpful in alleviating tardive dyskinesia may be more useful if person is on oral drug therapy.
本研究旨在监测口服临床推荐剂量氟哌啶醇引发的锥体外系症状（EPS），并将其与腹腔注射动物研究中所用剂量药物时产生的EPS进行比较。每天以1mg/kg的剂量给大鼠注射氟哌啶醇，持续5周，大鼠在旷场中表现出运动不能，运动协调性受损。从治疗的第2至5周，药物对运动协调性而非旷场运动不能的影响逐渐减弱。以临床推荐剂量将氟哌啶醇添加到饮用水中口服，大鼠的探索活动减少，但未产生运动不能。治疗3周后运动协调性受损最大，治疗5周后对药物诱导的运动损伤产生耐受性。口服氟哌啶醇时，空嚼运动（VCMs）和迟发性VCMs的强度比腹腔注射更大。目前的结果表明，预期产生持续效应的口服氟哌啶醇可能会导致急性帕金森样效应产生耐受性，但迟发性运动障碍的强度更大。我们建议，如果患者正在接受口服药物治疗，可能有助于减轻迟发性运动障碍的药物可能更有用。
