Verhagen-Kamerbeek W D, Hazemeijer I, Korf J, Lakke J P
Department of Neurology, University of Groningen, The Netherlands.
J Neural Transm Park Dis Dement Sect. 1993;6(1):17-26. doi: 10.1007/BF02252619.
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.
除了多巴胺能神经传递受损外，帕金森病中还存在去甲肾上腺素能系统功能失调。L-苏式-3,4-二羟基苯丝氨酸（DOPS）是去甲肾上腺素（NA）的合成前体，似乎对治疗帕金森病患者的一些运动不能症状有效。在本研究中，以氟哌啶醇诱导大鼠僵住症作为帕金森病运动不能的模型，研究了DOPS的可能作用。给雄性Wistar大鼠（240 - 290克）静脉输注NA（1.5和15微克/千克）或DOPS（2和4毫克/千克）可显著减轻僵住症。外周脱羧酶抑制剂苄丝肼（2毫克/千克）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预处理可增强并延长DOPS的抗僵住症作用。这些发现提示NA介导的抗僵住症作用的外周位点。只有在没有外周脱羧酶抑制剂的情况下，DOPS治疗才可能成功。此外，COMT抑制可能增强DOPS的治疗效果。
