{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:16:32Z","timestamp":1791936992434,"version":"4.3.4"},"reference-count":38,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T00:00:00Z","timestamp":1756771200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diseases"],"abstract":"<jats:p>Tavapadon, a novel oral dopamine-D1R\/D5R partial agonist, has been studied in recent years for the treatment of late-stage development Parkinson\u2019s disease (PD). Levodopa, a dopamine precursor that currently remains the gold-standard first-line therapy for PD motor symptoms, serves as a benchmark against emerging dopaminergic agents. By selectively activating D1-family receptors on direct-pathway medium neurons, Tavapadon differs in that it delivers levodopa-level motor benefit while avoiding its many D2R\/D3R-mediated adverse effects. In placebo-controlled trials, Tavapadon produced clear, clinically meaningful gains in motor function and day-to-day activities, as captured by the Unified Parkinson\u2019s Disease Rating Scale (UPDRS). Recent late-stage results have revealed that Tavapadon maintains superior UPDRS outcomes in de novo patients and, when added to levodopa, extended \u201cON\u201d time periods of reliable motor control free of troublesome dyskinesia, without introducing new safety concerns. In studies, nausea, headache, and somnolence were the most frequent adverse events. Hallucinations, orthostatic hypotension, and impulse-control disorders remained comparable to placebo, reflecting minimal D2R\/D3R-mediated effects. Preclinical primate studies have demonstrated levodopa-like motor rescue with markedly less dyskinesia, a pattern mirrored in clinical add-on trials. Collectively, evidence indicates that Tavapadon can match levodopa-mediated symptomatic efficacy, lower dyskinesia liability compared with levodopa or earlier full D1 receptor (D1R) agonists, and offer the convenience of once-daily dosing characteristics, which may bridge the therapeutic gap between levodopa and the current D2R\/D3R agonists in PD management. In the present investigation, the emerging clinical role for Tavapadon is described, along with the mechanism of action, clinical efficacy, safety, and future directions.<\/jats:p>","DOI":"10.3390\/diseases13090290","type":"journal-article","created":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T12:04:28Z","timestamp":1756814668000},"page":"290","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Emerging Clinical Role of Tavapadon, a Novel Dopamine Partial Agonist, in the Treatment of Parkinson\u2019s Disease"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2464-0187","authenticated-orcid":false,"given":"Alan D.","family":"Kaye","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Louisiana State University Health Sciences Center at Shreveport, Shreveport, LA 71103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-8766-8678","authenticated-orcid":false,"given":"Bennett M.","family":"Ford","sequence":"additional","affiliation":[{"name":"School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brennan M.","family":"Abbott","sequence":"additional","affiliation":[{"name":"School of Medicine, Louisiana State University Health Sciences Center at Shreveport, Shreveport, LA 71103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kalob M.","family":"Broocks","sequence":"additional","affiliation":[{"name":"School of Medicine, Louisiana State University Health Sciences Center at Shreveport, Shreveport, LA 71103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia","family":"Novacic","sequence":"additional","affiliation":[{"name":"School of Medicine, Louisiana State University Health Sciences Center at Shreveport, Shreveport, LA 71103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4545-4523","authenticated-orcid":false,"given":"Sahar","family":"Shekoohi","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Louisiana State University Health Sciences Center at Shreveport, Shreveport, LA 71103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Augustine, A., Winstanley, C.A., and Krishnan, V. (2021). Impulse Control Disorders in Parkinson\u2019s Disease: From Bench to Bedside. Front. Neurosci., 15.","DOI":"10.3389\/fnins.2021.654238"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"476","DOI":"10.2174\/1871527322666230331121028","article-title":"Rationale and Development of Tavapadon, a D1\/D5-Selective Partial Dopamine Agonist for the Treatment of Parkinson\u2019s Disease","volume":"23","author":"Bezard","year":"2024","journal-title":"CNS Neurol. Disord. Drug Targets"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1007\/s00702-025-02893-4","article-title":"Levodopa treatment: Impacts and mechanisms throughout Parkinson\u2019s disease progression","volume":"132","author":"Riederer","year":"2025","journal-title":"J. Neural Transm."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1670","DOI":"10.1001\/jama.2014.3654","article-title":"Pharmacological Treatment of Parkinson Disease: A Review","volume":"311","author":"Connolly","year":"2014","journal-title":"JAMA"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1212\/WNL.0000000000012868","article-title":"Dopaminergic Therapy for Motor Symptoms in Early Parkinson Disease Practice Guideline Summary: A Report of the AAN Guideline Subcommittee","volume":"97","author":"Pringsheim","year":"2021","journal-title":"Neurology"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Servillo, F., De Carluccio, M., Di Lazzaro, G., Campanelli, F., Marino, G., Natale, G., Ledonne, A., Cenere, M.M., Paldino, E., and Di Giuda, D. (2024). Molecular and cellular determinants of L-Dopa-induced dyskinesia in Parkinson\u2019s Disease. NPJ Park. Dis., 10.","DOI":"10.1038\/s41531-024-00836-6"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1146\/annurev-neuro-061010-113641","article-title":"Modulation of Striatal Projection Systems by Dopamine","volume":"34","author":"Gerfen","year":"2011","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"155","DOI":"10.3390\/receptors3020009","article-title":"Dopamine D1\u2013D5 Receptors in Brain Nuclei: Implications for Health and Disease","volume":"3","author":"IKawahata","year":"2024","journal-title":"Receptors"},{"key":"ref_9","unstructured":"Choi, J., and Horner, K.A. (2025, June 30). Dopamine Agonists, StatPearls, Available online: http:\/\/www.ncbi.nlm.nih.gov\/books\/NBK551686\/."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1001\/archneur.58.2.249","article-title":"Induction by Dopamine D1 Receptor Agonist ABT-431 of Dyskinesia Similar to Levodopa in Patients with Parkinson Disease","volume":"58","author":"Rascol","year":"2001","journal-title":"Arch. Neurol."},{"key":"ref_11","first-page":"1515","article-title":"The D1\/D5 Dopamine Partial Agonist PF-06412562 in Advanced-Stage Parkinson\u2019s Disease: A Feasibility Study","volume":"10","author":"Huang","year":"2020","journal-title":"J. Park. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Mailman, R.B., Yang, Y., and Huang, X. (2021). D1, not D2, dopamine receptor activation dramatically improves MPTP-induced parkinsonism unresponsive to levodopa. Eur. J. Pharmacol., 892.","DOI":"10.1016\/j.ejphar.2020.173760"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Lewis, M.M., Van Scoy, L.J., De Jesus, S., Hakun, J.G., Eslinger, P.J., Fernandez-Mendoza, J., Kong, L., Yang, Y., Snyder, B.L., and Loktionova, N. (2023). Dopamine D1 Agonists: First Potential Treatment for Late-Stage Parkinson\u2019s Disease. Biomolecules, 13.","DOI":"10.3390\/biom13050829"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Gray, D.L., Allen, J.A., Mente, S., O\u2019cOnnor, R.E., DeMarco, G.J., Efremov, I., Tierney, P., Volfson, D., Davoren, J., and Guilmette, E. (2018). Impaired \u03b2-arrestin recruitment and reduced desensitization by non-catechol agonists of the D1 dopamine receptor. Nat. Commun., 9.","DOI":"10.1038\/s41467-017-02776-7"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Teng, X., Chen, S., Nie, Y., Xiao, P., Yu, X., Shao, Z., and Zheng, S. (2022). Ligand recognition and biased agonism of the D1 dopamine receptor. Nat. Commun., 13.","DOI":"10.1038\/s41467-022-30929-w"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1021\/acschemneuro.9b00589","article-title":"D1 Agonist Improved Movement of Parkinsonian Nonhuman Primates with Limited Dyskinesia Side Effects","volume":"11","author":"Young","year":"2020","journal-title":"ACS Chem. Neurosci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1007\/s00702-018-1841-0","article-title":"Levodopa-induced dyskinesia in Parkinson\u2019s disease: Still no proof? A meta-analysis","volume":"125","author":"Giannakis","year":"2018","journal-title":"J. Neural Transm."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1007\/s40120-018-0114-z","article-title":"Phase 1 Parkinson\u2019s Disease Studies Show the Dopamine D1\/D5 Agonist PF-06649751 is Safe and Well Tolerated","volume":"7","author":"Sohur","year":"2018","journal-title":"Neurol. Ther."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Riesenberg, R., Werth, J., Zhang, Y., Duvvuri, S., and Gray, D. (2020). PF-06649751 efficacy and safety in early Parkinson\u2019s disease: A randomized, placebo-controlled trial. Ther. Adv. Neurol. Disord., 13.","DOI":"10.1177\/1756286420911296"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Fernandez, H., Isaacson, S., Hauser, R., Agarwal, P., Ondo, W., Park, A., Elmer, L., Kremens, D., Leoni, M., and Duvvuri, S. (2025). Efficacy and Safety of Tavapadon, an Orally Administered, Once-daily, Selective D1\/D5 Partial Dopamine Agonist, Adjunctive to Levodopa for Treatment of Parkinson\u2019s Disease with Motor Fluctuations (S37.003). Neurology, 104.","DOI":"10.1212\/WNL.0000000000208468"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Kreutzer, J., DeLuca, J., and Caplan, B. (2017). Unified Parkinson\u2019s Disease Rating Scale. Encyclopedia of Clinical Neuropsychology, Springer International Publishing.","DOI":"10.1007\/978-3-319-56782-2"},{"key":"ref_22","unstructured":"Cerevel Therapeutics (2025, May 12). LLC, A Phase 3, Double-Blind, Randomized, Placebo-Controlled, Parallel-Group, 27-Week Trial to Evaluate the Efficacy, Safety, and Tolerability of Two Fixed Doses of Tavapadon in Early Parkinson\u2019s Disease (TEMPO-1 TRIAL). Clinical Trial Registration NCT04201093, July 2024, Available online: https:\/\/clinicaltrials.gov\/study\/NCT04201093."},{"key":"ref_23","unstructured":"AbbVie News Center (2025, May 12). AbbVie Announces Positive Topline Results from Phase 3 TEMPO-1 Trial Evaluating Tavapadon as a Monotherapy for Parkinson\u2019s Disease. Available online: 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."},{"key":"ref_24","unstructured":"AbbVie News Center (2025, May 12). AbbVie Announces Positive Topline Results for the Phase 3 TEMPO-2 Trial Evaluating Tavapadon as a Monotherapy for Parkinson\u2019s Disease. Available online: 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."},{"key":"ref_25","unstructured":"AbbVie (2025, May 12). A Phase 3, Double-Blind, Randomized, Placebo-Controlled, Parallel-Group, Flexible-Dose, 27-Week Trial to Evaluate the Efficacy, Safety, and Tolerability of Tavapadon as Adjunctive Therapy for Parkinson\u2019s Disease in Levodopa-Treated Adults with Motor Fluctuations (TEMPO-3 Trial). clinicaltrials.gov, Clinical Trial Registration NCT04542499, Apr, Available online: https:\/\/clinicaltrials.gov\/study\/NCT04542499."},{"key":"ref_26","unstructured":"AbbVie (2025, May 12). 58-Week Open-Label Trial of Tavapadon in Parkinson\u2019s Disease (TEMPO-4 Trial). clinicaltrials.gov, Clinical Trial Registration NCT04760769, Mar, Available online: https:\/\/clinicaltrials.gov\/study\/NCT04760769."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"S580","DOI":"10.1002\/mds.22037","article-title":"Pharmacokinetics and pharmacodynamics of levodopa","volume":"23","author":"Nutt","year":"2008","journal-title":"Mov. Disord."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1177\/08971900221151194","article-title":"Monroe-Duprey, A Review of Levodopa Formulations for the Treatment of Parkinson\u2019s Disease Available in the United States","volume":"37","author":"Livingston","year":"2024","journal-title":"J. Pharm. Pract."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Pastino, G., Yuan, J., Duvvuri, S., Leoni, M., Largay, K., Chang, I., Giugliano, A., Versavel, S., Gray, D., and Sanchez, R. (2022). Pharmacokinetics, Pharmacodynamics, and Safety of the Highly Selective Dopamine D1\/D5 Agonist Tavapadon: Summary of Phase 1 Clinical Studies (P10-11.001). Neurology, 98.","DOI":"10.1212\/WNL.98.18_supplement.2728"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1002\/jcph.1096","article-title":"MAO-B and COMT Genetic Variations Associated with Levodopa Treatment Response in Patients with Parkinson\u2019s Disease","volume":"58","author":"Sampaio","year":"2018","journal-title":"J. Clin. Pharmacol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1177\/02698811241261022","article-title":"Three paradoxes related to the mode of action of pramipexole: The path from D2\/D3 dopamine receptor stimulation to modification of dopamine-modulated functions","volume":"38","author":"Szabadi","year":"2024","journal-title":"J. Psychopharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Sivanandy, P., Leey, T.C., Xiang, T.C., Ling, T.C., Han, S.A.W., Semilan, S.L.A., and Hong, P.K. (2021). Systematic Review on Parkinson\u2019s Disease Medications, Emphasizing on Three Recently Approved Drugs to Control Parkinson\u2019s Symptoms. Int. J. Environ. Res. Public Health, 19.","DOI":"10.3390\/ijerph19010364"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1038\/s41582-024-01034-x","article-title":"Parkinson disease therapy: Current strategies and future research priorities","volume":"20","author":"Stocchi","year":"2024","journal-title":"Nat. Rev. Neurol."},{"key":"ref_34","unstructured":"Stoker, T.B., and Greenland, J.C. (2025, May 12). Pharmacological Treatment of Parkinson\u2019s Disease, Parkinson\u2019s Disease: Pathogenesis and Clinical Aspects, Available online: http:\/\/www.ncbi.nlm.nih.gov\/books\/NBK536726\/."},{"key":"ref_35","unstructured":"AbbVie (2025, May 12). A Phase 3, Double-Blind, Randomized, Placebo-Controlled, Parallel-Group, Flexible-Dose, 27-Week Trial to Evaluate the Efficacy, Safety, and Tolerability of Tavapadon in Early Parkinson\u2019s Disease (TEMPO-2 Trial). Clinical Trial Registration NCT04223193, April 2025, Available online: https:\/\/clinicaltrials.gov\/study\/NCT04223193."},{"key":"ref_36","unstructured":"AbbVie News Center (2025, May 12). Cerevel Therapeutics Announces Positive Topline Results for Tavapadon in Phase 3 Adjunctive Trial for People Living with Parkinson\u2019s Disease. Available online: 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."},{"key":"ref_37","unstructured":"(2025, May 12). Tavapadon in Parkinson Disease\u2014Clinical Trials Registry\u2014ICH GCP. Available online: https:\/\/ichgcp.net\/clinical-trials-registry\/NCT04760769."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.1517\/14656566.7.10.1399","article-title":"The levodopa wearing-off phenomenon in Parkinson\u2019s disease: Pharmacokinetic considerations","volume":"7","author":"Stocchi","year":"2006","journal-title":"Expert Opin. Pharmacother."}],"container-title":["Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-9721\/13\/9\/290\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:37:51Z","timestamp":1760035071000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-9721\/13\/9\/290"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,2]]},"references-count":38,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["diseases13090290"],"URL":"https:\/\/doi.org\/10.3390\/diseases13090290","relation":{},"ISSN":["2079-9721"],"issn-type":[{"value":"2079-9721","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,2]]}}}