Attenuation of haloperidol-induced catalepsy by noradrenaline and L-threo-DOPS.

W D Verhagen-Kamerbeek, I Hazemeijer, J Korf, J P Lakke
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引用次数: 14

Abstract

In addition to impaired dopaminergic neurotransmission a dysfunctional noradrenergic system has been demonstrated in Parkinson's disease. L-threo-3,4-dihydroxyphenylserine (DOPS), a synthetic precursor of noradrenaline (NA), appears to be effective in the treatment of some akinetic symptoms in parkinsonian patients. In the present study the possible effect of DOPS was studied in rats, in which catalepsy was induced with haloperidol as a model for parkinsonian akinesia. Intravenous infusion of NA (1.5 and 15 micrograms/kg) or DOPS (2 and 4 mg/kg) in male Wistar rats (240-290 g) significantly decreased catalepsy. The effect of DOPS was abolished by pretreatment with the peripheral decarboxylase inhibitor benserazide (2 mg/kg). Pretreatment with Ro 40-7592, a catechol-O-methyltransferase inhibitor, potentiated and prolonged the anticataleptic effect of DOPS. The findings suggest a peripheral site of NA mediated anticataleptic action. Therapy with DOPS may be successful only without a peripheral decarboxylase inhibitor. Moreover, the therapeutic effect of DOPS may be potentiated by COMT inhibition.

去甲肾上腺素和l-三苯胺对氟哌啶醇致猝厥的抑制作用。
除了多巴胺能神经传递受损外,帕金森病还存在去甲肾上腺素能系统功能障碍。l -三o-3,4-二羟基苯基丝氨酸(DOPS)是去甲肾上腺素(NA)的合成前体,似乎可有效治疗帕金森病患者的一些动力学症状。本研究以氟哌啶醇致帕金森运动障碍大鼠为模型,研究DOPS的可能作用。雄性Wistar大鼠静脉输注NA(1.5和15微克/公斤)或DOPS(2和4毫克/公斤)(240-290克)可显著减轻麻痹。外周脱羧酶抑制剂苯塞拉肼(2mg /kg)预处理可消除DOPS的作用。儿茶酚- o -甲基转移酶抑制剂Ro 40-7592预处理可增强和延长DOPS的抗癫痫作用。研究结果提示NA介导的外周抗癫痫作用。只有在不使用外周脱羧酶抑制剂的情况下,DOPS治疗才可能成功。此外,DOPS的治疗效果可能通过抑制COMT而增强。
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