Chemistry:Tavapadon

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Tavapadon, sold under the brand name Juvmo, is a dopamine receptor agonist used for the treatment of Parkinson's disease.[1][2][3][4] It is taken orally.[1][5]

Medical uses

Tavapadon is indicated for the treatment of Parkinson's disease in adults.[1]

Available forms

Tavapadon is available in the form of 0.25 mg, 1 mg, 5 mg, 10 mg, and 15 mg oral tablets.[1]

Contraindications

Tavapadon has no contraindications.[1] Warnings and precautions include side effects of tavapadon like hypotension and orthostatic hypotension, impulse control or compulsive behaviors, hallucinations or psychotic-like behavior especially with strong CYP3A4 inhibitors, and dyskinesia.[1] Use of tavapadon with strong CYP3A4 inducers is not recommended.[1]

Side effects

Side effects of tavapadon may include nausea, headache, dizziness, fatigue or asthenia, dysgeusia, vomiting, dry mouth, and anxiety.[1] Other potential but less common side effects include hypotension, orthostatic hypotension, impulsive control problems, compulsive behaviors, hallucinations, psychotic-like behaviors, and dyskinesia.[1] Examples of impulse control problems include new or increased urges for gambling, sex, uncontrolled spending, binge or compulsive eating, and others.[1] The risk of hallucinations appears to be greater with older age.[1] About 20% of people discontinued tavapadon due to side effects, 85% of those during titration or adjustment phases.[1]

Interactions

Tavapadon is substrate for CYP3A4 and hence interacts with CYP3A4 inhibitors and inducers.[1] In addition to being a CYP3A4 substrate, tavapadon is a CYP3A4 inducer and can interact with CYP3A4 substrates.[1] It is also a CYP2C8 inhibitor and can interact with CYP2C8 substrates.[1] Tavapadon is a BCRP inhibitor and can interact with substrates of this protein as well.[1]

Pharmacology

Pharmacodynamics

Tavapadon acts as a highly selective partial agonist of the dopamine D1 receptor (Ki = 9 nM; IA = 65%) and the dopamine D5 receptor (Ki = 13 nM; IA = 81%).[3][4][5] It has no significant affinity or functional activity at the D2-like receptors (D2, D3, D4) (Ki ≥ 4,870 to 6,720 nM).[5] Tavapadon also shows biased agonism for Gs-coupled signaling at the D1-like receptors.[5][3]

Pharmacokinetics

Peak levels of tavapadon are reached after approximately 2 to 4 hours with oral administration.[1] It shows dose-proportional pharmacokinetics across its maintenance dosage range.[1] Food does not significantly modify the pharmacokinetics of tavapadon and it can be taken without regard for food.[1] The volume of distribution of tavapadon is 63.5 L.[1] Its plasma protein binding is 93%, primarily to albumin.[1] Tavapadon is primarily metabolized by CYP3A4.[1] It has a major inactive metabolite.[1] Unchanged tavapadon is excreted less than 1% in urine and feces.[1] Its major inactive metabolite was excreted less than 5% in urine and feces.[1] The elimination half-life of tavapadon is 25.5 hours.[1]

History

Tavapadon was developed by Cerevel Therapeutics, which acquired tavapadon from Pfizer in 2018.[2] It was approved for medical use in the United States in September 2026.[6][7]

Society and culture

Names

Tavapadon is the generic name of the drug and its INN and USAN.[8]

Tavapadon is not a controlled substance in the United States.[1]

Research

Tavapadon has not been formally developed for any indication besides Parkinson's disease.[2]

See also

References

  1. ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 1.14 1.15 1.16 1.17 1.18 1.19 1.20 1.21 1.22 1.23 1.24 1.25 1.26 https://www.rxabbvie.com/pdf/juvmo_pi.pdf
  2. ↑ 2.0 2.1 2.2 "Tavapadon - Cerevel Therapeutics". Adis Insight. Springer Nature Switzerland AG. https://adisinsight.springer.com/drugs/800039248. 
  3. ↑ 3.0 3.1 3.2 "An update on the use of non-ergot dopamine agonists for the treatment of Parkinson's disease". Expert Opinion on Pharmacotherapy 21 (18): 2279–2291. December 2020. doi:10.1080/14656566.2020.1805432. PMID 32804544. 
  4. ↑ 4.0 4.1 "Novel Strategies To Activate the Dopamine D1 Receptor: Recent Advances in Orthosteric Agonism and Positive Allosteric Modulation". Journal of Medicinal Chemistry 62 (1): 128–140. January 2019. doi:10.1021/acs.jmedchem.8b01767. PMID 30525590. 
  5. ↑ 5.0 5.1 5.2 5.3 "Rationale and Development of Tavapadon, a D1/D5-Selective Partial Dopamine Agonist for the Treatment of Parkinson's Disease". CNS Neurol Disord Drug Targets 23 (4): 476–487. 2024. doi:10.2174/1871527322666230331121028. PMID 36999711. "Tavapadon is a highly selective partial agonist at D1 and D5 dopamine receptors, [52] with little to no functional activity at D2, D3, or D4 receptors in vitro (unpublished data). Assays measuring the displacement of radioligand binding in cell lines expressing recombinant human dopamine receptors have shown that tavapadon has a high affinity for both D1 (Ki = 9 nM) and D5 (Ki = 13 nM) (unpublished data). Conversely, tavapadon had a low affinity at D2 (Ki ≥ 6210 nM), D3 (Ki ≥ 6720 nM), and D4 (Ki ≥ 4870 nM) (unpublished data). [...] In vitro assays of functional activity have confirmed that tavapadon acts as a partial agonist by binding at D1 and D5 receptors, corresponding to 65% and 81% of dopamine's intrinsic activity, respectively, and inducing functional receptor activation, with half-maximal effective concentration (EC50) values of 19 nM and 17 nM (unpublished data).". 
  6. ↑ "U.S. FDA Approves AbbVie's JUVMO™ (tavapadon) for Parkinson's Disease" (in en-US). 2026-09-28. https://www.biospace.com/press-releases/u-s-fda-approves-abbvies-juvmo-tavapadon-for-parkinsons-disease. 
  7. ↑ Research, Center for Drug Evaluation and (2026-09-25). "Novel Drug Approvals for 2026" (in en). FDA (FDA). https://www.fda.gov/drugs/novel-drug-approvals-fda/novel-drug-approvals-2026. 
  8. ↑ "Tavapadon". https://pubchem.ncbi.nlm.nih.gov/compound/86764100. 



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