Department of Neuroscience, University of Pisa, Pisa, Italy.
Parkinsonism Relat Disord. 2009 Dec;15 Suppl 4:S44-53. doi: 10.1016/S1353-8020(09)70835-1.
In the last two decades, the usefulness of dopamine receptor agonists in the symptomatic treatment of Parkinson' disease (PD) has been demonstrated in many randomized controlled clinical trials. The initial role of such compounds as an adjunctive therapy to L-dopa to improve motor fluctuations has now expanded to the treatment of early PD as initial monotherapy. The rationale for the use of dopamine receptor agonists in early disease is to delay or reduce the incidence of motor complications resulting from long-term L-dopa therapy, probably by virtue of less pulsatile stimulation of postsynaptic dopamine receptors. Indeed, controlled trials with both ergot and non-ergot dopamine receptor agonists, such as cabergoline, pergolide, pramipexole and ropinirole, have shown lower risk of motor fluctuations and dyskinesias than with L-dopa, when used as monotherapy in early PD patients. The benefit of agonists in preventing motor complications is, however, balanced by a smaller effect on motor symptoms compared with L-dopa. Moreover, a greater incidence of side-effects, particularly somnolence, hallucinations and leg oedema, occurs with dopamine receptor agonists. Because of the risk of fibrotic reactions, ergot derivatives (bromocriptine, cabergoline, and pergolide) are not recommended as first-line antiparkinsonian medication. In younger patients, who are usually more prone to developing L-dopa-induced motor complications, the initial treatment with dopamine receptor agonists can be recommended. Further pharmacological refinement of PD management with these drugs may result from new formulations of old drugs, such as once-daily prolonged-release ropinirole, or new agonists, such as the rotigotine patch, that can allow more continuous dopaminergic stimulation and improve patient compliance with the drug treatment. Theoretically, another advantage of dopamine receptor agonists is the potential for a neuroprotective effect, through many different mechanisms of actions. Preliminary controlled trials with pramipexole and ropinirole, although encouraging, did not provide conclusive proof of the disease-modifying effect of dopamine receptor agonists; large controlled clinical trials are now underway and results are expected soon.
在过去的二十年中，许多随机对照临床试验已经证明了多巴胺受体激动剂在帕金森病（PD）症状治疗中的有效性。这些化合物最初作为左旋多巴辅助治疗的作用已经扩展到早期 PD 的初始单一疗法。在早期疾病中使用多巴胺受体激动剂的原理是延迟或减少长期左旋多巴治疗引起的运动并发症的发生率，这可能是由于对突触后多巴胺受体的更非脉冲刺激。事实上，与左旋多巴相比，使用培高利特、卡麦角林、普拉克索和罗匹尼罗等非麦角类多巴胺受体激动剂进行的对照试验表明，在早期 PD 患者中作为单一疗法，运动波动和运动障碍的风险较低。然而，与左旋多巴相比，激动剂在预防运动并发症方面的益处被其对运动症状的影响较小所抵消。此外，多巴胺受体激动剂的副作用发生率更高，特别是嗜睡、幻觉和腿部水肿。由于纤维性反应的风险，麦角衍生物（溴隐亭、卡麦角林和培高利特）不推荐作为一线抗帕金森病药物。在年轻患者中，通常更容易出现左旋多巴引起的运动并发症，因此可以推荐使用多巴胺受体激动剂进行初始治疗。这些药物对 PD 管理的进一步药理学改进可能来自于旧药物的新配方，如每日一次的延长释放普拉克索，或新的激动剂，如罗替高汀贴片，这些药物可以允许更持续的多巴胺刺激，并提高患者对药物治疗的依从性。从理论上讲，多巴胺受体激动剂的另一个优势是通过许多不同的作用机制具有潜在的神经保护作用。虽然普拉克索和罗匹尼罗的初步对照试验令人鼓舞，但并未提供多巴胺受体激动剂对疾病具有修饰作用的确凿证据；目前正在进行大型对照临床试验，预计很快会有结果。
