Hasegawa K
Division of Neurology, Sagamihara National Hospital.
Nihon Rinsho. 2000 Oct;58(10):2066-71.
The purpose of the new drugs for Parkinson's disease is control of the long-term levodopa treatment syndromes, especially wearing-off phenomenon and dyskinesia. Therefore, they show long T1/2. Most of them are classified into dopamine agonists. Others are monoamine oxidase B inhibitor and cathecole-o-methyltransferase inhibitor. Marketed dopamine agonists are bromocriptine, pergolide, talipexole, and cabergoline in Japan. Except talipexole, they are all ergot alkaloid derivatives. Their affinity for dopamine receptor is D2 group, and their T1/2 are longer than levodopa. Bromocriptine is an oldest dopamine agonist. Other 3 drugs and bromocriptine had made each other double blinded cross over trial previously. The result of double blinded studies show that their efficacy for PD treatment were equal, 40-50% patients with PD. However, in clinical usage, some difference is observed as described below. Efficacy of pergolide is strong compared with bromocriptine; however, pergolide is easy to arise dyskinesia. Talipexole is strong in the hypnosis effect. As for cabergoline, it takes long time to show medical effect, so that it is expected to control wearing-off phenomenon. Monoamine oxidase B inhibitor, Selegiline, is useful as an economizer effect to levodopa. As for the cathechole-o-methyltransferase inhibitor (COMT-I) will be make double-blinded trial in future. The efficacy for PD treatment of COMT-I is prolonged levodopa effect for PD, so that wearing-off phenomenon will be controlled. To use these drugs successfully is important with the treatment of PD. In the future, the development of the cause therapy in addition to the systematic therapy is wanted.
治疗帕金森病的新药旨在控制长期左旋多巴治疗引起的综合征,尤其是疗效减退现象和运动障碍。因此,它们的半衰期较长。其中大多数被归类为多巴胺激动剂。其他的是单胺氧化酶B抑制剂和儿茶酚-O-甲基转移酶抑制剂。在日本上市的多巴胺激动剂有溴隐亭、培高利特、他利克索和卡麦角林。除他利克索外,其余均为麦角生物碱衍生物。它们对多巴胺受体的亲和力属于D2类,半衰期比左旋多巴长。溴隐亭是最早的多巴胺激动剂。之前,其他3种药物与溴隐亭进行了相互双盲交叉试验。双盲研究结果表明,它们对帕金森病的治疗效果相当,40%-50%的帕金森病患者有效。然而,在临床应用中,观察到了如下一些差异。培高利特的疗效比溴隐亭强,但容易引发运动障碍。他利克索的催眠作用较强。至于卡麦角林,起效时间较长,有望控制疗效减退现象。单胺氧化酶B抑制剂司来吉兰可作为左旋多巴的增效剂。儿茶酚-O-甲基转移酶抑制剂(COMT-I)未来将进行双盲试验。COMT-I对帕金森病的治疗效果是延长左旋多巴对帕金森病的作用,从而控制疗效减退现象。成功使用这些药物对帕金森病的治疗很重要。未来,除了系统性治疗外,还需要开展病因治疗的研究。