Protective effect of L-type calcium channel blockers against haloperidol-induced orofacial dyskinesia: A behavioural, biochemical and neurochemical study

被引:13
作者
Bishnoi, Mahendra [1 ]
Chopra, Kanwaljit [2 ]
Kulkarni, Shrinivas K. [1 ,2 ]
机构
[1] Panjab Univ, CPEBS, Chandigarh 160014, India
[2] Panjab Univ, Univ Inst Pharmaceut Sci, Div Pharmacol, Chandigarh 160014, India
关键词
calcium channel blockers; haloperidol; neurochemical; tardive dyskinesia;
D O I
10.1007/s11064-008-9660-6
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Haloperidol is a classical neuroleptic drug that is still in use and can lead to abnormal motor activity such as tardive dyskinesia (TD) following repeated administration. TD has no effective therapy yet. There is involvement of calcium in triggering the oxidative damage and excitotoxicity, both of which play central role in haloperidol-induced orofacial dyskinesia and associated alterations. The present study was carried out to investigate the protective effect of calcium channel blockers [verapamil (10 and 20 mg/kg), diltiazem (10 and 20 mg/kg), nifedipine (10 and 20 mg/kg) and nimodipine (10 and 20 mg/kg)] against haloperidol induced orofacial dyskinesia and associated behavioural, biochemical and neurochemical alterations in rats. Chronic administration of haloperidol (1 mg/kg i.p., 21 days) resulted in a significant increase in orofacial dyskinetic movements and significant decrease in % retention, coupled with the marked increase in lipid peroxidation and superoxide anion generation where as significant decrease in non protein thiols and endogenous antioxidant enzyme (SOD and catalase) levels in rat brain striatum homogenates. All these deleterious effects of haloperidol were significantly attenuated by co-administration of different calcium channel blockers. Neurochemically, chronic administration of haloperidol resulted in significant decrease in levels of catecholamines (dopamine, serotonin) and their metabolites (HVA and HIAA) but increased turnover of dopamine and serotonin. Co-administration of most effective doses of verapamil, diltiazem, nifedipine and nimodipine significantly attenuated these neurochemical changes. Results of the present study indicate that haloperidol-induced calcium ion influx is involved in the pathogenesis of tardive dyskinesia and calcium channel blockers should be tested in clinical trials with nifedipine as the most promising one.
引用
收藏
页码:1869 / 1880
页数:12
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