Glutamatergic, noradrenergic, serotonergic, and cholinergic systems play a critical role in the basal ganglia circuitry. Targeting these non-dopaminergic receptors remains a focus of ongoing research to improve Parkinson’s disease (PD) motor symptoms, without the potential side effects of dopamine replacement therapy. This review updates advancements in non-dopaminergic treatments for motor control in PD since 2013. To date, no non-dopaminergic selective drug has shown significant long-term efficacy as monotherapy in PD. The largest area of development in non-dopaminergic targets has been for motor complications of dopamine replacement therapy (motor fluctuations and dyskinesia). For treatment of motor fluctuations, safinamide, zonisamide, and istradefylline are currently approved, and novel glutamatergic and serotonergic drugs are in development. Long-acting formulations of amantadine are approved for treating dyskinesia. Several non-dopaminergic drugs have failed to show anti-dyskinetic efficacy, while some are still in development. Non-dopaminergic targets are also being pursued to treat specific motor symptoms of PD. For example, CX-8998 (a calcium channel modulator) is being evaluated for PD tremor and rivastigmine may improve gait dysfunction in PD. Drug repurposing continues to be a key strategy for non-dopaminergic targets in PD, but the field needs to increase discovery and availability of such drugs.

谷氨酸能、去甲肾上腺素能、血清素能和胆碱能系统在基底神经节回路中起关键作用。针对这些非多巴胺能受体仍然是正在进行的研究的重点，以改善帕金森病 (PD) 运动症状，而没有多巴胺替代疗法的潜在副作用。本综述更新了自 2013 年以来用于 PD 运动控制的非多巴胺能治疗的进展。迄今为止，没有一种非多巴胺能选择性药物在 PD 中作为单一疗法显示出显着的长期疗效。非多巴胺能靶标的最大发展领域是多巴胺替代疗法的运动并发症（运动波动和运动障碍）。用于治疗运动波动，safinamide、唑尼沙胺和 istradefylline 目前已获批准，并且正在开发新型谷氨酸能和血清素能药物。金刚烷胺的长效制剂被批准用于治疗运动障碍。一些非多巴胺能药物未能显示出抗运动障碍的功效，而一些仍在开发中。非多巴胺能靶点也正在寻求治疗 PD 的特定运动症状。例如，CX-8998（一种钙通道调节剂）正在评估 PD 震颤，而利凡斯的明可能会改善 PD 的步态功能障碍。药物再利用仍然是 PD 中非多巴胺能靶点的关键策略，但该领域需要增加此类药物的发现和可用性。例如，CX-8998（一种钙通道调节剂）正在评估 PD 震颤，而利凡斯的明可能会改善 PD 的步态功能障碍。药物再利用仍然是 PD 中非多巴胺能靶点的关键策略，但该领域需要增加此类药物的发现和可用性。例如，CX-8998（一种钙通道调节剂）正在评估 PD 震颤，而利凡斯的明可能会改善 PD 的步态功能障碍。药物再利用仍然是 PD 中非多巴胺能靶点的关键策略，但该领域需要增加此类药物的发现和可用性。