Calne D B, Burton K, Beckman J, Martin W R
Can J Neurol Sci. 1984 Feb;11(1 Suppl):221-4. doi: 10.1017/s0317167100046448.
Dopamine agonists have yielded two important advances to our understanding of the basal ganglia--they have facilitated the subdivision of different classes of dopamine receptors, and they have established the fact that important dopaminergic effects can be achieved by activation of dopamine receptors in a manner that is unrelated to anoxal impulse traffic in dopaminergic neurons--a phenomenon similar in its diffuse, slow, characteristics to an endocrine effect. The tangible clinical benefit of dopamine agonists has been evident in patients with prominent dyskinesia or wearing off reactions. It is possible that earlier use of agonists, in low doses combined with similarly low doses of levodopa, may improve the long term treatment of Parkinson's disease, but as yet there is no firm evidence. In the future, we can expect to see agonists with more prolonged effects, deriving from the formation of active metabolites. We can also hope to gain further insight into the correlations between the various animal models of dopaminomimetic activity, and specific aspects of drug efficacy and toxicity in parkinsonian patients. Such information should allow the design of improved pharmacotherapy.
多巴胺激动剂在我们对基底神经节的理解方面取得了两项重要进展——它们促进了不同类别的多巴胺受体的细分,并且证实了通过激活多巴胺受体能够产生重要的多巴胺能效应,这种方式与多巴胺能神经元中的无轴突冲动传递无关——这一现象在其弥散、缓慢的特征上类似于内分泌效应。多巴胺激动剂在患有明显运动障碍或药效减退反应的患者中具有显著的临床益处。早期低剂量使用激动剂并联合同样低剂量的左旋多巴,有可能改善帕金森病的长期治疗,但目前尚无确凿证据。未来,我们有望看到具有更长作用时间的激动剂,这源于活性代谢产物的形成。我们也希望能进一步深入了解多巴胺模拟活性的各种动物模型之间的相关性,以及帕金森病患者药物疗效和毒性的具体方面。这些信息应有助于设计出更优的药物治疗方案。