一款CNS药物从靶点验证到抵达患者，于迎行业仍在探索更多治疗路径，被低仍有许多未被满足的估年个方治疗需求。在中枢神经系统（CNS）疾病药物研发中，向终转载授权请在「药明康德」微信公众号回复“转载”，于迎作为多巴胺前体，被低它能为患者补充缺失的估年个方多巴胺信号，通过平行人工膜渗透模型（PAMPA）、向终艾伯维（AbbVie）的于迎D1/D5受体部分激动剂Juvmo（tavapadon）获FDA批准上市，脑组织及脑脊液中的被低分布与游离浓度，助力全球合作伙伴加速CNS候选药物从靶点验证走向临床转化。估年个方
此次获批的向终Juvmo（tavapadon）的特别之处，都依赖于科学认知的提升与研发能力的持续积累。早在上世纪八九十年代，帮助合作伙伴降低CNS项目早期风险，更将一个坐了三十多年冷板凳的老靶点，这个分子不同于完全激动剂，安全性评价与转化研究的一体化CNS药物发现支持体系，与此同时，如果能精准激活多巴胺系统的特定受体，他们推测问题或许并不出在受体本身，显著缓解运动症状。加速突破血脑屏障带来的研发瓶颈，
编者按：自上世纪60年代左旋多巴问世以来，其中，
权属备注：欢迎个人转发至朋友圈，到分子设计策略的迭代，每一步突破，是其中较为成熟的一条路线，帕金森病领域始终在等待新机制疗法的到来。利用原位脑灌注与脑微透析等先进技术，它是一个高选择性的D1/D5受体部分激动剂，单纯给大脑"补多巴胺"并非终极策略，日前，
图片来源：123RF
更多方向助力帕金森病治疗
Tavapadon的成功验证了D1/D5通路的治疗价值，其激活与促进运动相关。FDA官网显示，支持小分子、但一进入人体就暴露出问题：有些分子口服生物利用度差、又不至于把受体推到过度激活、靶向D1样受体的策略却进展缓慢。它也表明CNS新药研发是一场漫长的接力赛，它让D1受体被过度激活，
理论上，这也代表着主动免疫策略在临床试验中显示出延缓帕金森病进展的潜力。具有治疗潜力"的分子。不仅意味着帕金森病患者多了一种新的多巴胺受体激动剂选择，
为了弥补早期完全激动剂的缺陷，到Cerevel的临床试验开展，体内评价与机制解析的一体化药代动力学研究策略，主动免疫策略也在推进。
在中枢神经系统疾病药物研发中，药明康德将持续以一体化研发赋能平台，并在药效学、药明康德DMPK建立了系统化的分级评估体系：在早期阶段，复杂的病理机制与血脑屏障等生物学挑战，生物标志物检测及PK/PD关联研究，如需获得治疗方案指导，对疗效、
不过，然而随着治疗需求的提升，成瘾行为及疼痛相关功能学评价，即后来的tavapadon。这场跨越三家公司的产业接力，包括D1和D5受体，平台能够将疾病模型数据与转化科学紧密结合，
这些结果让科学家意识到，仍有一些科学家没有放弃对D1样受体的探索。每一棒都需要跨越大量专业关卡。文中观点不代表药明康德立场，D5亚型）是理想候选者。MDR1-MDCK细胞模型等高通量体外模型，让更多创新疗法更快抵达患者身边。快速筛选具备脑渗透潜力的候选分子。精神疾病、100%的受试者产生了针对目标抗原的免疫应答，支持从分子设计到临床转化的跨尺度决策。需要发挥部分激动剂的作用。需要回答一连串问题：能否穿透血脑屏障，
多巴胺能系统之外，药明康德生物学业务平台（WuXi Biology）构建了覆盖药效评估、也可能比老一代分子更契合临床长期用药的实际需求。癫痫、回望来路，但在漫长的时间里，团队还把它打磨成适合长期用药的形式，并结合学习记忆、TEMPO系列3期试验的接连成功，药明康德药物代谢与动力学部（DMPK）围绕CNS构建了覆盖体外筛选、不是"更猛烈地激活它"，今年3月，生物大分子及新型疗法的开发。受体占有率分析、D1样受体（包括D1、AC Immune的在研疫苗ACI-7104在早期帕金森病患者中开展的2期VacSYn试验取得积极的中期结果，再到艾伯维推进FDA申报并最终获得批准，药明康德药物代谢与动力学部（DMPK）围绕CNS构建了覆盖体外筛选、让一支专门聚焦中枢神经系统的团队来推进这个"机制独特、LRRK2靶向疗法、新一代A2A拮抗剂仍在临床探索中。例如腺苷A2A受体拮抗剂、辉瑞（Pfizer）的研发团队意识到，D1受体主要表达于纹状体直接通路神经元，使得临床前阶段对模型预测性与转化能力提出更高要求。并减少OFF时间。安全性评价与转化研究的一体化CNS药物发现支持体系，或许能更精细地调控运动信号。作为对神经科学管线的一次前瞻性布局，而是"更聪明地激活它"。可为全球合作伙伴提供从早期机制验证到候选分子推进的系统性解决方案。始终面临着复杂的病理机制与血脑屏障等各类生物学挑战。
接力推动tavapadon走向前台
2023年12月，但帕金森病药物研发的版图远不止于此，行业正从多个维度寻找更多能惠及患者的新疗法。随着对受体药理学理解的加深，TEMPO-3试验率先显示，
D1样受体是多巴胺受体家族的重要亚类，快速脱敏的位置。再到临床开发的高效推进，用于治疗成人帕金森病，Tavapadon随之进入Cerevel管线，要真正发挥D1样受体的潜力，非多巴胺能靶点也是重要的探索方向。ALS）、艾伯维向美国FDA提交tavapadon的新药申请，
针对D1样受体，结构优化及转运机制研究相结合，推到了具有治疗意义的前台。为什么一个重要的靶点会沉寂这么多年？Tavapadon又是怎么把它重新激活的？
图片来源：123RF
被“冷落”三十年的靶点
上世纪六十年代，药明康德DMPK能够帮助客户系统性提升CNS候选药物的脑暴露预测准确性，药明康德生物学业务平台（WuXi Biology）构建了覆盖药效评估、Kyowa Kirin的istradefylline已获批用于帕金森病的辅助治疗，实现对认知与神经功能的综合分析。
2018年，让它可口服、并持续维持至第28天。
这些挫折使D1样受体药物开发一度降温，tavapadon的症状评分较安慰剂组取得统计学显著改善。目前礼来将其开发方向列为症状性阿尔茨海默病。推动创新疗法更高效地迈向临床。
但要如何解决这一问题呢？
图片来源：123RF
打通被低估的路径
在这一探索路程中，获取转载须知。揭示真实脑暴露水平。依托这一"分层筛选+多模型验证+机制驱动优化"的综合能力，2024年4月，作为早期帕金森病的单药治疗时，早在30多年前就被认为是帕金森病治疗的潜力靶点。
与此同时，抗α-突触核蛋白疗法等，两个试验均达到主要终点。在接受左旋多巴治疗并出现运动波动的中晚期帕金森病患者中，这个曾被寄予厚望的靶点，但激活受体的强度又低于内源性多巴胺。为D1/D5选择性部分激动策略提供了更系统的临床证据。
但在主流判断之外，可为全球合作伙伴提供从早期机制验证到候选分子推进的系统性解决方案。谢绝媒体或机构未经授权以任何形式转载至其他平台。因此，
After 30 Years of Being Underestimated, This Approach Finally Has an FDA-Approved Drug
Since the introduction of levodopa in the 1960s, dopamine replacement strategies have remained a cornerstone of Parkinson’s disease treatment. Yet as treatment needs have evolved, the field has continued to seek therapies with novel mechanisms. The FDA recently approved AbbVie’s D1/D5 receptor partial agonist Juvmo (tavapadon) for the treatment of Parkinson’s disease in adults, adding a new treatment option that selectively modulates D1/D5 receptor signaling. At the same time, the industry continues to explore other therapeutic approaches, including adenosine A2A receptor antagonists, LRRK2-targeted therapies, and therapies targeting α-synuclein, further broadening the Parkinson’s disease R&D landscape.
Drug discovery for central nervous system (CNS) diseases, however, continues to face major biological challenges, including complex disease mechanisms and the blood-brain barrier. To address these industry needs, WuXi Biology, a business unit of WuXi AppTec, has built an integrated CNS drug discovery support system spanning efficacy assessment, safety evaluation, and translational research, providing global clients with systematic solutions from early mechanism validation to candidate advancement. WuXi AppTec DMPK has established an integrated pharmacokinetic research strategy around CNS that covers in vitro screening, in vivo evaluation, and mechanistic analysis, enabling global clients to accelerate the path from target validation to late-stage research for CNS drug candidates.
The significance of the newly approved Juvmo (tavapadon) goes beyond giving people with Parkinson’s disease another dopamine receptor agonist option. It also represents progress along a therapeutic path that had long been regarded as difficult to pursue successfully: targeting D1-like receptors.
D1-like receptors are an important subclass of the dopamine receptor family and include the D1 and D5 receptors. They were recognized more than 30 years ago as potential therapeutic targets in Parkinson’s disease, yet drug development against these receptors progressed slowly for decades. Why did such an important target remain on the sidelines for so long? And how did tavapadon bring this approach back into focus?
Image source: 123RF
A Target Sidelined for Three Decades
The introduction of levodopa in the 1960s transformed the treatment of Parkinson’s disease. As a dopamine precursor, levodopa helps restore deficient dopaminergic signaling and can substantially improve motor symptoms. With long-term treatment, however, many patients gradually develop motor fluctuations and drug-induced dyskinesia.
These limitations prompted researchers to consider whether simply “adding dopamine” to the brain was sufficient as a long-term strategy. More selective activation of specific receptors within the dopamine system could, in principle, enable finer control of motor signaling.
D1-like receptors, including the D1 and D5 subtypes, emerged as attractive candidates. In particular, D1 receptors are predominantly expressed on neurons in the striatal direct pathway, where their activation is associated with the facilitation of movement. As early as the 1980s and 1990s, several full agonists targeting D1-like receptors entered development. Although some improved motor function in animal models, substantial challenges emerged in humans. Some compounds had poor oral bioavailability and required injection, while others could be given orally but were associated with hypotension, motor disturbances, and other tolerability or safety concerns.
These setbacks caused enthusiasm for D1-like receptor drug development to decline. Pharmacokinetic and tolerability limitations associated with early full agonists became major development barriers, leaving this once-promising target on the sidelines for nearly three decades.
Still, some researchers continued to explore D1-like receptor pharmacology. As understanding of receptor signaling advanced, they began to consider whether the problem lay not with the receptor itself, but with the full-agonist strategy.
A full agonist can be compared to pressing an accelerator all the way down: strong receptor activation can drive an intense biological response, leaving relatively little room between the desired pharmacological effect and unwanted effects.
So how could that problem be addressed?
Image source: 123RF
Unlocking an Underestimated Pathway
During this period of exploration, Pfizer researchers pursued a different approach. Instead of seeking stronger activation of D1-like receptors, the strategy shifted toward more controlled activation through partial agonism. Based on this concept, Pfizer identified a candidate initially known as PF-06649751, which would later become tavapadon.
Pharmacologically, tavapadon is a highly selective D1/D5 receptor partial agonist. It has substantially greater affinity for D1/D5 receptors than for other dopamine receptor subtypes, while producing less receptor activation than a full agonist. Conceptually, this is more like adjusting the accelerator to an appropriate level rather than pressing it fully down—providing sufficient receptor activation to improve motor function while reducing the risk of excessive stimulation.
The molecule was also optimized for chronic treatment, including oral administration and once-daily dosing. Its development was intended in part to address tolerability issues, such as hypotension, that had limited earlier D1/D5 full agonists. These advances suggested that partial agonism could offer not only a pharmacologically viable approach, but also one better suited to the practical requirements of long-term treatment.
▲The molecular structure of tavapadon (Image source：PubChem)
In 2018, Pfizer and Bain Capital established Cerevel Therapeutics, a company focused on CNS drug development, creating a dedicated organization to advance this mechanistically differentiated molecule. Tavapadon subsequently became part of Cerevel’s pipeline and entered the pivotal TEMPO Phase 3 clinical development program.
A Relay Effort Brings Tavapadon to the Forefront
In December 2023, AbbVie announced an agreement to acquire Cerevel for approximately $8.7 billion as part of an expansion of its neuroscience pipeline, with tavapadon among the key assets.
In April 2024, the TEMPO-3 trial reported positive results in patients with more advanced Parkinson’s disease who were receiving levodopa and experiencing motor fluctuations. As an adjunct to levodopa, tavapadon significantly increased “ON” time without troublesome dyskinesia and reduced “OFF” time.
AbbVie completed its acquisition of Cerevel in August 2024. Over the following months, TEMPO-1 and TEMPO-2 also met their primary endpoints. When evaluated as monotherapy in early Parkinson’s disease, tavapadon produced statistically significant improvements in symptom scores compared with placebo. Together, the TEMPO studies provided further clinical support for the feasibility of selectively targeting D1/D5 receptors with a partial agonist.
In September 2025, AbbVie submitted a New Drug Application for tavapadon to the U.S. FDA, ultimately leading to its approval. Looking back, the path from Pfizer’s early pharmacological concept to Cerevel’s clinical development program and ultimately to AbbVie’s FDA submission and approval represents an industry relay across three companies that brought the medicine through regulatory review.
Tavapadon therefore offers not only a new mechanism-based treatment option for Parkinson’s disease, but also renewed clinical relevance for a receptor pathway that had faced development challenges for more than three decades.
Image source: 123RF
Expanding Therapeutic Directions in Parkinson’s Disease
The success of tavapadon supports the therapeutic value of the D1/D5 pathway, but Parkinson’s disease drug development extends well beyond this mechanism. The industry is pursuing multiple approaches in search of additional therapies that may benefit patients.
Within the D1 receptor field, Eli Lilly and Company has developed mevidalen (LY3154207), a positive allosteric modulator (PAM) of the D1 receptor. Rather than directly occupying the dopamine-binding site, mevidalen enhances activation of the D1 receptor by endogenous dopamine. The molecule was previously studied in Parkinson’s disease dementia and dementia with Lewy bodies; Lilly currently lists mevidalen in its pipeline for symptomatic Alzheimer’s disease.
Beyond the dopaminergic system, non-dopaminergic targets represent another important area of investigation. Adenosine A2A receptor antagonists modulate the basal ganglia indirect pathway through a non-dopaminergic mechanism and represent one of the more established approaches in this category. Kyowa Kirin’s istradefylline has already been approved as adjunctive therapy for Parkinson’s disease, while next-generation A2A receptor antagonists continue to be explored clinically.
LRRK2-targeted therapies represent another direction. LRRK2 mutations are among the most common genetic causes of familial Parkinson’s disease, and abnormal pathway activity has also been observed in sporadic disease. Targeting LRRK2 may therefore offer a way to intervene more directly in disease biology.
In March 2026, Arvinas reported Phase 1 clinical data for its LRRK2 protein degrader ARV-102. In patients with Parkinson’s disease, ARV-102 reduced cerebrospinal fluid LRRK2 levels by approximately 50% or more at Day 14 across all dose levels, with the reductions maintained through Day 28.
Moving beyond symptom control toward slowing disease progression is another important goal in Parkinson’s disease research. Targeting α-synuclein is among the most closely watched disease-modifying strategies. In addition to passive antibody approaches, active immunization is also being explored.
AC Immune’s investigational active immunotherapy ACI-7104 recently generated positive week-100 results from Part 1 of the Phase 2 VacSYn trial in patients with early Parkinson’s disease. The study met all primary endpoints, with a 100% immune response rate after three immunizations, antibody penetration into cerebrospinal fluid, and signals of target engagement. These findings support further investigation of active immunization as a potential disease-modifying strategy in Parkinson’s disease.
Integrated Platform Supports Global CNS Drug Development
The development of tavapadon illustrates the long path from molecular design to clinical development. It also highlights why CNS drug R&D can resemble a long relay race, with each stage presenting distinct technical challenges.
For a CNS drug to progress from target validation toward patient use, researchers must answer a series of fundamental questions. Can the molecule cross the blood-brain barrier and achieve sufficient unbound drug concentrations in the brain? Can it act on the intended target with an acceptable safety profile?
In central nervous system (CNS) drug discovery, complex disease biology and biological barriers such as the blood–brain barrier (BBB) impose significant challenges, placing higher demands on the predictive value and translational relevance of preclinical models. WuXi Biology has established an integrated CNS drug discovery support platform encompassing efficacy evaluation, safety assessment, and translational research, providing systematic solutions for global clients from early mechanism validation through candidate advancement.
Leveraging strong in vivo pharmacology capabilities, the platform has developed a comprehensive set of disease models covering neurodegenerative disorders (such as Alzheimer’s disease, Parkinson’s disease, and ALS), psychiatric disorders, epilepsy, multiple sclerosis, and stroke. Combined with functional assessments including learning and memory, social behavior, addiction-related behavior, and pain-related endpoints, the platform enables comprehensive evaluation of cognitive and neurological functions.
WuXi Biology also integrates electroencephalogram monitoring, receptor occupancy analysis, biomarker evaluation, and PK/PD correlation studies to support multi-endpoint assessment of efficacy, safety, and target engagement, enabling the development of small molecules, biologics, and emerging therapeutic modalities. Supported by AAALAC-accredited animal facilities and standardized experimental systems, the platform closely links disease model data with translational science, improving late-stage predictability and development efficiency, helping clients reduce early-stage risk in CNS programs and accelerate the advancement of innovative therapies toward late-stage development.
In addition, WuXi AppTec DMPK has established an integrated pharmacokinetic strategy to address a central challenge in central nervous system (CNS) drug development: enabling sufficient brain penetration while maintaining effective exposure. To overcome the restrictive nature of the BBB, WuXi AppTec DMPK has built a tiered and systematic evaluation framework spanning in vitro screening, in vivo assessment, and mechanistic understanding.
At the early stage, high-throughput in vitro models, including parallel artificial membrane permeability assay (PAMPA) and MDR1-MDCK cell systems, are combined with transporter studies and physicochemical profiling to efficiently identify compounds with brain penetration potential. At the in vivo stage, techniques such as in situ brain perfusion and brain microdialysis are employed to quantitatively assess drug distribution and unbound concentrations in plasma, brain tissue, and cerebrospinal fluid, enabling accurate determination of key parameters such as the unbound brain-to-plasma partition coefficient (Kp,uu) and providing a true reflection of brain exposure.
In parallel, WuXi AppTec DMPK integrates pharmacokinetic data with physiologically based pharmacokinetic (PBPK) modeling, structure optimization, and transporter mechanism studies to support cross-scale decision-making from molecular design to clinical translation. Through this comprehensive “tiered screening + multi-model validation + mechanism-driven optimization” approach, WuXi AppTec DMPK empowers clients to improve the predictability of CNS drug exposure, overcome BBB-related development challenges, and accelerate the advancement of innovative therapies toward the clinic.
In Parkinson’s disease and across the broader CNS field, many treatment needs remain unmet. From revisiting targets, to iterating molecular design strategies, to optimizing late-stage development, each step forward depends on deeper scientific understanding and sustained accumulation of research and discovery capabilities. Looking ahead, WuXi AppTec will continue to leverage its integrated platform to support global clients in CNS drug discovery, helping more innovative therapies reach patients faster.
Key Takeaways:
The FDA approval of Juvmo (tavapadon) adds a new D1/D5 receptor-targeted option for adults with Parkinson’s disease. The approval brings renewed clinical relevance to a receptor pathway that has faced substantial development challenges for more than three decades.
Partial agonism provides a different way to revisit D1-like receptor pharmacology. Tavapadon was designed to provide selective, controlled activation of D1/D5 receptors while addressing pharmacokinetic and tolerability limitations that complicated the development of earlier full agonists.
Parkinson’s disease R&D is expanding across multiple mechanisms. Current approaches include D1 receptor positive allosteric modulators, adenosine A2A receptor antagonists, LRRK2-targeted therapies, and active immunization strategies targeting α-synuclein, with growing interest in approaches that may go beyond symptom control.
CNS drug development continues to face major translational challenges. Blood-brain barrier penetration, sufficient unbound brain exposure, target engagement, safety, and the predictive value of preclinical models remain important considerations throughout development.
WuXi AppTec provides end-to-end enabling capabilities for CNS drug discovery. WuXi Biology offers an integrated platform spanning efficacy evaluation, safety assessment, and translational research, with a broad portfolio of neurological disease models and functional endpoints. WuXi AppTec DMPK has built an integrated CNS pharmacokinetic strategy to help clients accelerate CNS candidates from target validation through late-stage research and toward the clinic.
参考资料：
[1] Bain Capital and Pfizer Create Cerevel Therapeutics, New CNS Company. Retrieved September 9, 2026 from https://www.baincapital.com/news/bain-capital-and-pfizer-create-cerevel-therapeutics-new-cns-company
[2] Cerevel Therapeutics Announces Positive Topline Results for Tavapadon in Phase 3 Adjunctive Trial for People Living with Parkinson's Disease. Retrieved September 9, 2026 from https://news.abbvie.com/2024-04-18-Cerevel-Therapeutics-Announces-Positive-Topline-Results-for-Tavapadon-in-Phase-3-Adjunctive-Trial-for-People-Living-with-Parkinsons-Disease
[3] AbbVie Completes Acquisition of Cerevel Therapeutics. Retrieved September 9, 2026 from https://news.abbvie.com/2024-08-01-AbbVie-Completes-Acquisition-of-Cerevel-Therapeutics
[4] AbbVie Announces Positive Topline Results from Phase 3 TEMPO-1 Trial Evaluating Tavapadon as a Monotherapy for Parkinson's Disease. Retrieved September 9, 2026 from https://news.abbvie.com/2024-09-26-AbbVie-Announces-Positive-Topline-Results-from-Phase-3-TEMPO-1-Trial-Evaluating-Tavapadon-as-a-Monotherapy-for-Parkinsons-Disease
[5] AbbVie Announces Positive Topline Results for the Phase 3 TEMPO-2 Trial Evaluating Tavapadon as a Monotherapy for Parkinson's Disease. Retrieved September 9, 2026 from https://news.abbvie.com/2024-12-09-AbbVie-Announces-Positive-Topline-Results-for-the-Phase-3-TEMPO-2-Trial-Evaluating-Tavapadon-as-a-Monotherapy-for-Parkinsons-Disease
[6] AbbVie Submits New Drug Application to U.S. FDA for Tavapadon for the Treatment of Parkinson's Disease. Retrieved September 9, 2026 from https://news.abbvie.com/2025-09-26-AbbVie-Submits-New-Drug-Application-to-U-S-FDA-for-Tavapadon-for-the-Treatment-of-Parkinsons-Disease
[7] Arvinas Announces Positive Phase 1 Data for ARV-102 Showing Greater Than 50% Reduction in Cerebrospinal Fluid LRRK2. Retrieved September 9, 2026 from https://ir.arvinas.com/news-releases/news-release-details/arvinas-announces-positive-phase-1-data-arv-102-showing-greater/
[8] Novel Drug Approvals for 2026. Retrieved September 26, 2026, from https://www.fda.gov/drugs/novel-drug-approvals-fda/novel-drug-approvals-2026
[9] US FDA approves AbbVie's drug for Parkinson's disease. Retrieved September 26, 2026, from https://www.reuters.com/business/healthcare-pharmaceuticals/us-fda-approves-abbvies-drug-parkinsons-disease-2026-09-25/
[10] AbbVie Submits New Drug Application to U.S. FDA for Tavapadon for the Treatment of Parkinson's Disease. Retrieved September 26, 2026, from https://news.abbvie.com/2025-09-26-AbbVie-Submits-New-Drug-Application-to-U-S-FDA-for-Tavapadon-for-the-Treatment-of-Parkinsons-Disease
免责声明：本文仅作信息交流之目的，WuXi Biology通过脑电图监测、
▲Tavapadon分子结构（图片来源：PubChem）
原理上，针对血脑屏障（BBB）这一关键生物屏障对药物分布的严格限制，作为左旋多巴辅助治疗，体内评价与机制解析的一体化药代动力学研究策略。礼来（Eli Lilly and Company）开发的mevidalen（LY3154207）走的是D1受体正变构调节剂（PAM）路线，
多发性硬化及脑卒中等在内的多维动物模型体系，社会行为、在脑内达到足够的游离药物浓度？能否精准作用且足够安全？正是基于这样的行业需求，在散发患者中也被观察到通路活性异常，艾伯维宣布以约87亿美元收购Cerevel，辉瑞团队最初筛选出了一个名为PF-06649751的候选分子，从早期辉瑞提出的突破性思路，其开发也意在改善早期D1/D5完全激动剂所面临的低血压等耐受性问题。它不直接结合多巴胺位点，安全性及靶点作用进行多终点整合评估，请前往正规医院就诊。实时定量检测药物在血浆、建立了涵盖神经退行性疾病（如阿尔茨海默病、
帕金森病乃至更广泛的CNS疾病领域，信号过强，也为帕金森病治疗增加了通过选择性调节D1/D5受体发挥作用的新选择。从靶点的重新认识，腺苷A2A受体拮抗剂通过非多巴胺能机制调节基底节间接通路，而是出在"完全激动剂"这个策略上。
同时，支持一天一次给药；同时，随后进入了一段长达近三十年的"冷板凳"期。提高临床预测性与研发效率，平台依托完善的体内药理学能力，多巴胺替代策略一直是帕金森病治疗的支柱。需要注射给药；有些虽可口服，助力全球合作伙伴的CNS新药研发过程，运动障碍等安全性问题。却伴随低血压、这些设计上的进展，早期完全激动剂面临的药代和耐受性问题成为主要开发瓶颈。是帕金森病研发中的重要目标之一。除被动抗体外，而就在这之后的数月，加速创新疗法迈向临床阶段。
从控制症状走向延缓疾病进展，基于这一思路，
完全激动剂的作用方式，Mevidalen此前曾在帕金森病痴呆和路易体痴呆中开展临床研究，LRRK2靶向疗法代表了另一条思路。tavapadon可显著增加无令人困扰的异动症的ON时间，即对D1/D5受体的亲和力远高于其他多巴胺受体亚型，艾伯维完成对Cerevel的收购，靶点结合等多项指标上达成预设目标。tavapadon也在其中。LRRK2基因突变是家族性帕金森病最常见的遗传病因之一，意味着部分激动剂策略不仅在理论上行得通，ARV-102在所有给药剂量下均可在第14天实现脑脊液LRRK2水平约50%或以上的降低，Tavapadon不仅为帕金森病治疗带来了一款新机制的药物选择，并启动了关键的TEMPO系列3期临床试验。但长期使用后，在体内阶段，依托AAALAC认证动物设施与标准化实验体系，TEMPO-1与TEMPO-2也相继传来捷报，药明康德围绕CNS药物研发构建了从靶点验证到临床转化的系统性赋能能力。更在于它终于走通了一条过去被默认"行不通"的路：D1样受体。Arvinas公布了其LRRK2蛋白降解剂ARV-102的1期临床数据：在帕金森病患者中，
2025年9月，结合转运体研究与理化性质分析，辉瑞与贝恩资本合作成立了专注于CNS药物研发的 Therapeutics，药明康德DMPK将药代数据与基于生理学的药代动力学模型（PBPK）、并推动其最终获批。帕金森病、针对行业需求，患者会逐渐出现运动波动以及药物诱导的异动症。
此外，
一体化平台赋能全球CNS新药研发
Tavapadon的研发历程体现了CNS新药从分子设计到临床开发所经历的漫长链条，精准计算脑-血浆未结合分配系数（Kp,uu）等关键参数，亦不代表药明康德支持或反对文中观点。因此靶向LRRK2有望从机制层面延缓疾病进展。而是通过增强内源性多巴胺对D1受体的激活发挥作用。它们在动物模型里确实能改善运动功能，多个靶向D1样受体的完全激动剂进入了研发阶段，
同年8月，这相当于把"油门"精确调到既能改善运动、左旋多巴的出现为帕金森病患者带来了革命性的改善。疗效和副作用之间几乎没有缓冲区。
针对药物"入脑并维持暴露"的核心挑战，像是一脚把油门踩到底，本文也不是治疗方案推荐。未来，