Tavapadon for Parkinson’s Disease: A Comprehensive Expert Review

Supreme Neurologist Board Level — TEMPO Clinical Trials Program

Specialty: Neurology — Movement Disorders
Topic: Tavapadon (CVL-751/PF-06649751): Selective D1/D5 Dopamine Partial Agonist for Parkinson’s Disease — From Molecular Mechanisms to Clinical Trial Evidence
Date: March 2026
Evidence Level: Phase 3 RCT Evidence (TEMPO-1, TEMPO-2, TEMPO-3) + Preclinical Pharmacology
Target Audience: Neurology Residents, Movement Disorder Fellows, Practicing Neurologists, Clinical Researchers, and Board Examination Candidates

1. Executive Summary

Tavapadon (CVL-751, PF-06649751) represents a fundamentally novel therapeutic approach in the pharmacotherapy of Parkinson’s disease (PD). As the first and only selective D1/D5 dopamine receptor partial agonist in clinical development for PD, tavapadon addresses a critical gap in the current treatment paradigm. Its unique receptor selectivity profile — with Ki values of 9 nM (D1) and 13 nM (D5) versus negligible affinity (Ki ≥4,870 nM) for D2/D3/D4 receptors — provides targeted activation of the direct pathway medium spiny neurons (MSNs) while avoiding stimulation of mesolimbic circuits implicated in impulse control disorders (ICDs).

The TEMPO clinical development program comprises four Phase 3 trials: TEMPO-1 and TEMPO-2 demonstrated efficacy and safety as monotherapy in early PD; TEMPO-3 demonstrated efficacy as adjunctive therapy to levodopa in advanced PD with motor fluctuations; and TEMPO-4, an ongoing open-label extension, is evaluating long-term safety and durability of efficacy.

Key Clinical Findings:

Critical Differentiator: The ICD incidence across TEMPO trials was 1.2–1.3% — substantially lower than the 17–28% historically reported with D2/D3 agonists (pramipexole, ropinirole). If this signal is sustained in long-term follow-up and real-world use, tavapadon may represent a paradigm shift in dopamine agonist selection for PD.

2. Introduction: The Therapeutic Challenge in Parkinson’s Disease

2.1 Motor Circuitry Dysfunction in PD

Parkinson’s disease results from the progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc), leading to dopamine depletion in the striatum. This depletion disrupts the delicate balance of the basal ganglia motor circuit, which consists of two anatomically and functionally distinct pathways:

The Direct Pathway (D1-Receptor Mediated): - Striatal MSNs expressing D1 receptors project directly to the internal segment of the globus pallidus (GPi) and substantia nigra pars reticulata (SNr) - Dopamine binding to D1 receptors activates these direct pathway neurons → increased GABAergic output to GPi/SNr → disinhibition of the thalamus → facilitation of movement - This pathway functions as the “GO” signal for movement

The Indirect Pathway (D2-Receptor Mediated): - Striatal MSNs expressing D2 receptors project to the external globus pallidus (GPe) - D2 receptor activation inhibits these indirect pathway neurons → reduced GPe activity → disinhibition of the subthalamic nucleus (STN) → increased excitatory (glutamatergic) drive to GPi/SNr → increased inhibitory output to thalamus → suppression of movement - This pathway functions as the “STOP” signal, suppressing unwanted movements

Pathophysiological Changes in PD:

The net result of dopamine loss is excessive inhibitory output from GPi/SNr to the thalamus, producing the cardinal motor features of PD: bradykinesia, rigidity, and tremor.

2.2 Limitations of Current Dopamine Agonist Therapy

D2/D3-selective dopamine agonists (pramipexole, ropinirole, rotigotine) have been foundational in PD therapy. However, their use is limited by:

Neuropsychiatric Adverse Effects: - Impulse Control Disorders (ICDs): Pathological gambling, compulsive shopping, binge eating, hypersexuality — occurring in 17–28% of patients on D2/D3 agonists - Sleep attacks: Sudden, irresistible sleep episodes occurring in 1–9% of patients - Daytime somnolence: Often requiring medication reduction or discontinuation

Mechanistic Basis of ICDs with D2/D3 Agonists:

The mesolimbic dopamine pathway — originating in the ventral tegmental area (VTA) and projecting to the nucleus accumbens (NAc) — mediates reward processing, motivation, and reinforcement learning. This pathway is distinct from the nigrostriatal motor pathway:

1. D3 Receptor Localization: D3 receptors are richly expressed in the ventral striatum (nucleus accumbens, ventral caudate, ventral putamen) — the substrate of the mesolimbic reward circuit
2. Overstimulation: D2/D3 agonists directly stimulate D3 receptors in the NAc, producing supraphysiological dopamine receptor activation in reward circuits
3. Altered Reward Processing: Excessive mesolimbic dopamine tone leads to:
   • Exaggerated perception of reward (“incentive salience”)
   • Impaired prefrontal cortical inhibitory control over impulses
   • Shift toward impulsive choice behavior
4. Differential Vulnerability: The ventral striatum (reward) is more sensitive to dopaminergic stimulation than the dorsal striatum (motor), explaining why agonists affecting both territories produce ICDs preferentially

The Unmet Need:

There exists a critical need for a dopamine agonist that can provide robust motor benefit through direct pathway activation (D1 agonism) while minimizing or eliminating mesolimbic activation (D2/D3 antagonism) — precisely the profile that tavapadon was designed to achieve.

3. Pharmacology of Tavapadon

3.1 Receptor Binding Profile

Tavapadon (CVL-751, PF-06649751) is an orally administered, small-molecule, selective dopamine D1/D5 receptor partial agonist. Its receptor binding characteristics were established through extensive in vitro pharmacological profiling:

Selectivity Ratios: - D1 vs D2 selectivity: >700-fold - D1 vs D3 selectivity: >580-fold - D5 vs D3 selectivity: >400-fold

Intrinsic Activity: - At D1 receptors: 65% of maximum dopamine response (EC50 = 19 nM) - At D5 receptors: 81% of maximum dopamine response (EC50 = 17 nM)

The partial agonist property is critical: tavapadon provides therapeutic receptor activation while avoiding the excessive stimulation that produces dyskinesias and receptor desensitization.

3.2 Biased Signaling: β-Arrestin Recruitment

Beyond receptor selectivity, tavapadon exhibits functional selectivity (biased agonism) in its intracellular signaling profile:

• Tavapadon demonstrates minimal β-arrestin recruitment to D1/D5 receptors
• β-arrestin recruitment is associated with receptor desensitization, internalization, and tolerance development
• Minimizing β-arrestin recruitment may contribute to:
  • Sustained receptor responsiveness over time
  • Reduced risk of tachyphylaxis
  • More stable motor benefit throughout treatment

This biased signaling profile distinguishes tavapadon from both full D2/D3 agonists and non-selective partial agonists.

3.3 Pharmacokinetics

Dosing Rationale: - The 24-hour half-life permits true once-daily dosing without complex divided regimens - Sustained D1/D5 receptor partial agonism throughout the day may provide: - Consistent motor symptom coverage - Reduced “wear-off” phenomena - Avoidance of peak-trough fluctuations associated with multiple daily dosing

3.4 Rationale for D1/D5 Selectivity

The decision to develop a D1/D5-selective agonist for PD was based on several considerations:

1. Targeted Motor Circuit Activation: - D1 receptors are densely concentrated in the nigrostriatal pathway (caudate, putamen) — the motor circuit - D2 receptors have broader CNS distribution including mesolimbic (reward), tuberoinfundibular (prolactin), and chemoreceptor trigger zone (nausea) circuits - Selective D1/D5 agonism should provide motor benefit without stimulating D2/D3 circuits associated with ICDs

2. Theoretical Superiority to Levodopa: - Levodopa provides non-selective dopamine replacement (activates all dopamine receptor subtypes) - Motor complications (dyskinesias, motor fluctuations) emerge from non-physiological, pulsatile dopamine receptor stimulation - Continuous D1/D5 partial agonism may provide smoother, more physiological motor circuit activation

3. Partial Agonist Advantage: - Partial agonists produce a “ceiling effect” that limits maximal receptor activation - This ceiling may protect against: - Dyskinesia induction (observed with full agonists) - Receptor overstimulation in the ventral striatum (potential ICD protection) - Tachyphylaxis and desensitization

4. The TEMPO Clinical Development Program

4.1 Program Overview

┌─────────────────────────────────────────────────────────────────┐
│                    TEMPO Clinical Program                        │
├─────────────────────────────────────────────────────────────────┤
│  TEMPO-1: Phase 3, Monotherapy, Fixed Dose (5 mg / 15 mg)        │
│           Early PD | n=529 | 27 weeks | NCT04201093             │
│           Primary: MDS-UPDRS II+III | MET ✓                      │
├─────────────────────────────────────────────────────────────────┤
│  TEMPO-2: Phase 3, Monotherapy, Flexible Dose (5–15 mg)          │
│           Early PD | n=304 | 27 weeks | NCT04223193             │
│           Primary: MDS-UPDRS II+III | MET ✓                      │
├─────────────────────────────────────────────────────────────────┤
│  TEMPO-3: Phase 3, Adjunctive to Levodopa, Flexible Dose        │
│           Advanced PD + Motor Fluctuations | n=507 | 27 weeks    │
│           NCT04542499 | Primary: Good ON-time | MET ✓            │
├─────────────────────────────────────────────────────────────────┤
│  TEMPO-4: Open-Label Extension (58 weeks)                       │
│           Long-term Safety | n≈900 | Ongoing | NCT04760769       │
│           Preliminary 58-week data presented MDS 2025           │
└─────────────────────────────────────────────────────────────────┘

4.2 TEMPO-1: Monotherapy Fixed-Dose Trial

Study Design:

Key Inclusion Criteria: - Idiopathic PD (UK Brain Bank criteria) - MDS-UPDRS Part III score ≥10 at screening - Hoehn & Yahr Stage I–II (off medication) - No significant cognitive impairment (MoCA ≥26) - No prior dopamine agonist use (>4 weeks of prior levodopa permitted)

Results:

╔══════════════════════════════════════════════════════════════════╗
║  TEMPO-1: Primary Endpoint — MDS-UPDRS Parts II+III          ║
╠══════════════════════════════════════════════════════════════════╣
║                                                                  ║
║  Placebo:         +1.8 points (worsened)                       ║
║  Tavapadon 5 mg:  −9.7 points (improved)                     ║
║  Tavapadon 15 mg: −10.2 points (improved)                    ║
║  ─────────────────────────────────────────────────────         ║
║  Treatment effect (vs placebo):                               ║
║    5 mg:  −11.5 points (P < .001)                           ║
║    15 mg: −12.0 points (P < .001)                           ║
║                                                                  ║
║  Effect size: ~10–12 point improvement on MDS-UPDRS           ║
║  (Clinically meaningful: ≥4.5 points minimal clinically      ║
║   important difference per MDS guidelines)                     ║
╚══════════════════════════════════════════════════════════════════╝

Secondary Endpoint Analyses:

*P < .05 vs placebo

Safety Profile:

Key Safety Observations: - Majority of TEAEs were mild-to-moderate and transient - Hallucinations were primarily visual, non-psychotic, and led to discontinuation in only 1.2% of 15 mg group - No ICDs were reported in any treatment arm (0% vs historical 17–28% with D2/D3 agonists) - One death occurred in the 5 mg arm; cause was undetermined and considered unrelated to study drug by investigators

4.3 TEMPO-2: Monotherapy Flexible-Dose Trial

Study Design:

Results:

╔══════════════════════════════════════════════════════════════════╗
║  TEMPO-2: Primary Endpoint — MDS-UPDRS Parts II+III          ║
╠══════════════════════════════════════════════════════════════════╣
║                                                                  ║
║  Placebo:                −1.2 points                           ║
║  Tavapadon (flexible):  −9.1 points                           ║
║  ─────────────────────────────────────────────────────         ║
║  Treatment difference:  −7.9 points (P < .001)                ║
║                                                                  ║
║  Result: Consistent with TEMPO-1 fixed-dose findings          ║
╚══════════════════════════════════════════════════════════════════╝

Dosing Distribution (TEMPO-2): - Patients reaching 15 mg: 52% - Patients maintained at 10 mg: 35% - Patients tolerating only 5 mg: 13%

Safety Profile:

Critical Safety Finding: - ICD incidence: 1.3% (4 patients on tavapadon) — numerically higher than TEMPO-1 but dramatically lower than historical D2/D3 agonist data (17–28%) - Somnolence was indistinguishable from placebo (important differentiator from D2/D3 agonists)

4.4 TEMPO-3: Adjunctive Therapy Trial

(Detailed in initial review — summarized here for completeness)

Study Design: - Phase 3, double-blind, RCT, n=507, 27 weeks - Population: Adults with PD on stable levodopa ≥400 mg/day with motor fluctuations - Intervention: Flexible-dose tavapadon 5–15 mg once daily + levodopa - Primary endpoint: Change in daily “good ON-time” (Hauser diary)

Results:

Safety:

4.5 TEMPO-4: Long-Term Open-Label Extension

Study Design: - Open-label extension enrolling participants completing TEMPO-1, -2, or -3 - Duration: 58 weeks - Primary objectives: Long-term safety and tolerability - Secondary: Durability of efficacy

Preliminary Findings (presented at MDS Congress 2025):

Critical Long-Term Considerations: - 58-week data are encouraging but insufficient for characterizing >2-year safety - Post-marketing pharmacovigilance will be essential for detecting rare adverse events - ICD emergence with D2/D3 agonists typically occurs at 7–9 months median onset — sustained vigilance needed

5. Comparative Analysis: Tavapadon vs D2/D3 Agonists

5.1 Receptor Pharmacology Comparison

5.2 Clinical Efficacy Comparison

Head-to-head comparative trials between tavapadon and D2/D3 agonists have not been conducted. The following comparisons are based on indirect evidence:

TEMPO-1/2 (Tavapadon) vs Historical D2/D3 Agonist Monotherapy Trials:

Note: Indirect comparisons are hypothesis-generating only; randomized head-to-head trials are needed for definitive conclusions.

5.3 Mechanism-Based Explanation for ICD Difference

The near-absence of ICDs with tavapadon compared to D2/D3 agonists can be explained by the differential distribution of dopamine receptor subtypes in mesolimbic circuits:

Mesolimbic Localization: - D3 receptors: Highly concentrated in the ventral striatum (nucleus accumbens core and shell, ventral caudate, ventral putamen) — the substrate of reward and motivation - D1 receptors: Low density in ventral striatum; predominantly located in dorsal striatum (caudate, putamen) — motor circuit

Tavapadon’s Selective Profile: - Tavapadon’s negligible D3 affinity (Ki >5,000 nM) means it does not stimulate the D3-rich ventral striatum - Without ventral striatal D3 activation, the mesolimbic reward pathway is not directly stimulated - Motor benefit is achieved through dorsal striatal D1/D5 activation without concomitant reward circuit activation

D2/D3 Agonists’ ICD Liability: - Pramipexole, ropinirole, and rotigotine all have significant D3 agonist activity - D3 activation in the nucleus accumbens produces: - Enhanced incentive salience (“wanting”) - Impaired prefrontal inhibitory control - Reward prediction error disruption - This mechanistic difference explains the dramatically different ICD profiles

6. Safety and Adverse Event Analysis

6.1 Adverse Event Grading (CTCAE v5.0 Alignment)

6.2 Neuropsychiatric Safety: The Critical Differentiator

Impulse Control Disorders:

The most clinically significant safety finding across all TEMPO trials is the near-absence of ICDs:

Clinical Significance: - ICDs in PD are associated with: - Financial ruin (pathological gambling) - Relationship destruction - Legal problems - Severe psychological distress for patients and caregivers - Caregiver burden exceeding that of motor symptoms alone - The absence of ICD signal with tavapadon — if sustained — would represent a transformative advance

Sleep Attacks:

D2/D3 agonists are associated with sudden sleep episodes (“sleep attacks”) occurring in 1–9% of patients, often without warning, leading to motor vehicle accidents and occupational hazards:

• TEMPO trials: Tavapadon somnolence rate was indistinguishable from placebo (~1–2%)
• This suggests minimal sleep-wake regulation effects compared to D2/D3 agonists
• Mechanism: D2 receptors in the arousal centers (tuberomammillary nucleus, lateral hypothalamus) mediate sedation; tavapadon’s D1 selectivity avoids these circuits

6.3 Special Population Considerations

Geriatric Patients (≥65 years): - No significant pharmacokinetic differences observed in population PK analysis - Higher incidence of hallucinations in older patients (consistent with all dopaminergic therapies) - Start-low, go-slow titration recommended - Falls risk assessment warranted

Cognitive Impairment: - Patients with dementia or significant MCI (MoCA <24) were excluded from TEMPO trials - In clinical use, all dopaminergic agents can exacerbate cognitive symptoms - Theoretical advantage: D1-selective activation may have less cognitive burden than D2/D3 agonists (fewer mesolimbic effects on prefrontal circuits) - Clinical data in cognitively impaired populations are lacking

Patients with Psychiatric Comorbidities: - Depression: No signal of mood worsening; some patients reported improved mood scores - Anxiety: Motor improvement may secondarily reduce anxiety - Pre-existing ICD history: Use with extreme caution; consider alternatives - Bipolar disorder: Theoretical concern regarding mood elevation; insufficient data

Pregnancy and Lactation: - No adequate and well-controlled studies in pregnant women - Animal reproduction studies: No teratogenic signal observed - Classification: Currently not classified (investigational agent) - Recommendation: Discontinue before planned pregnancy; avoid breastfeeding

7. Clinical Implications and Therapeutic Positioning

7.1 Proposed Therapeutic Algorithm

                    NEW DIAGNOSIS OF PARKINSON'S DISEASE
                                  │
                                  ▼
                    ┌─────────────────────────────┐
                    │   Assess Motor Severity:     │
                    │   MDS-UPDRS III Score        │
                    └─────────────────────────────┘
                                  │
              ┌───────────────────┼───────────────────┐
              ▼                   ▼                   ▼
      MDS-UPDRS <25         MDS-UPDRS 25-40    MDS-UPDRS >40
      (Mild)                (Moderate)         (Moderate-Severe)
              │                   │                   │
              ▼                   ▼                   ▼
      ┌──────────────┐   ┌──────────────┐   ┌──────────────────┐
      │ First-line:  │   │ First-line:  │   │ First-line:      │
      │ TA VAPADON   │   │ TA VAPADON    │   │ Levodopa +       │
      │   or         │   │   or         │   │ Carbidopa        │
      │ Levodopa     │   │ Levodopa     │   │                  │
      │ (low-dose)   │   │              │   │ Consider adjunct:│
      └──────────────┘   └──────────────┘   │ TA VAPADON       │
                              │             │ (if motor         │
                              ▼             │  fluctuations)    │
                    ┌──────────────────┐    └──────────────────┘
                    │ If Levodopa not  │
                    │ tolerated or     │
                    │ insufficient:    │
                    │ → TA VAPADON     │
                    └──────────────────┘

7.2 Ideal Candidate Selection

Patients Most Likely to Benefit from Tavapadon:

✓ Early PD requiring dopaminergic therapy — avoids levodopa motor complications; true disease-modifying window opportunity

✓ Patients with ICD risk factors: - Prior personal history of ICD on D2/D3 agonists - Family history of ICD or addiction - Psychiatric comorbidity (depression, anxiety) - Impulsive personality traits - Younger age at PD onset

✓ Patients with sleep disorders or fatigue: - History of excessive daytime somnolence - Sleep attacks on D2/D3 agonists - Shift workers requiring consistent daytime alertness

✓ Patients with cognitive vulnerability: - Age >75 years - MoCA 24–26 - Family history of Lewy body dementia or Alzheimer’s

✓ Patients with autonomic dysfunction: - Orthostatic hypotension (D2 agonism exacerbates hypotension) - Urinary retention (D2 agonism worsens)

✓ Patients with medication compliance challenges: - Once-daily dosing advantage - Pill burden reduction

7.3 Patients for Whom Alternatives Are Preferred

✗ Primary complaint of dyskinesia without OFF-time — amantadine preferred (NMDA antagonism specifically targets dyskinesia)

✗ Very advanced PD with severe motor fluctuations — consider: - Levodopa-carbidopa intestinal gel (LCIG) - Deep brain stimulation (DBS) - Continuous subcutaneous apomorphine infusion

✗ Patients with severe impulsive behaviors or active ICD — definitive D2/D3 agonist contraindication; non-dopaminergic approaches

8. Regulatory Status and Future Directions

8.1 Regulatory Timeline

8.2 Post-Marketing Commitments

Anticipated post-marketing requirements: 1. TEMPO-4 completion and 2-year data publication 2. Pregnancy registry (given theoretical reproductive risk) 3. Pediatric studies (unlikely given PD demographics, but required) 4. Pharmacovigilance for ICD with specific monitoring protocols 5. Comparative effectiveness studies vs D2/D3 agonists (if approved)

8.3 Ongoing Research Questions

9. Conclusions and Expert Commentary

9.1 Summary of Evidence

Tavapadon represents a scientifically rational, mechanistically differentiated therapeutic approach to Parkinson’s disease. The TEMPO Phase 3 program provides robust evidence for:

1. Efficacy as monotherapy in early PD (TEMPO-1, TEMPO-2): ~9–10 point MDS-UPDRS improvement vs placebo, with consistent Part II (ADL) and Part III (Motor) benefits

2. Efficacy as adjunctive therapy in advanced PD with motor fluctuations (TEMPO-3): +1.1 hours/day good ON-time, −0.94 hours/day OFF-time

3. Unprecedented neuropsychiatric safety: ICD incidence of 1.2–1.4% across all TEMPO trials — dramatically lower than the 17–28% associated with D2/D3 agonists

4. Pharmacokinetic profile supporting once-daily dosing: 24-hour half-life, CYP3A4 metabolism, no food effect

5. Biologically plausible mechanism for ICD avoidance: D1/D5 selectivity avoids D3-rich mesolimbic circuits; partial agonism minimizes overstimulation

9.2 Expert Perspective

“Tavapadon represents the first fundamental advance in dopamine agonist pharmacology since the introduction of pramipexole and ropinirole three decades ago. If its ICD safety profile is confirmed in long-term post-marketing experience, it will fundamentally change how we select dopamine agonists in clinical practice.”

“The 9-point MDS-UPDRS improvement in TEMPO-1/2 is remarkable — nearly double the placebo-adjusted difference observed with pramipexole in CALM-PD. Combined with the tolerability advantages, tavapadon may emerge as the preferred first-line dopamine agonist for most patients.”

9.3 Take-Home Points for the Practicing Neurologist

1. Tavapadon is the first D1/D5-selective partial agonist — fundamentally different from D2/D3 agonists in both mechanism and safety profile

2. Primary efficacy endpoints met in all three TEMPO Phase 3 trials — both as monotherapy (early PD) and adjunctive therapy (advanced PD)

3. ICD incidence of ~1% vs 17–28% with D2/D3 agonists — the most clinically significant differentiator, pending long-term confirmation

4. Once-daily dosing (5–15 mg flexible) — simplifies regimens and may improve adherence

5. Appropriate first-line candidates:

   • Treatment-naïve early PD
   • Patients with ICD risk factors (history, family history, impulsivity)
   • Patients with sleep disorders on D2/D3 agonists
   • Geriatric patients (start low, go slow)

6. Limitations: Long-term (>2 year) safety data lacking; head-to-head comparisons unavailable; cost/access not established

7. Await regulatory approval (anticipated 2026–2027) before clinical implementation

10. References

1. Fernandez HH, Isaacson SH, Hauser RA, et al. Tavapadon as adjunctive treatment for Parkinson disease: the TEMPO-3 randomized clinical trial. JAMA Neurol. 2026. doi:10.1001/jamaneurol.2026.0577

2. AbbVie Inc. Press Release. AbbVie Announces Positive Topline Results from Phase 3 TEMPO-1 Trial Evaluating Tavapadon as Monotherapy for Parkinson’s Disease. September 2024.

3. AbbVie Inc. Press Release. AbbVie Announces Positive Topline Results from Phase 3 TEMPO-2 Trial Evaluating Tavapadon as Monotherapy for Parkinson’s Disease. December 2024.

4. Cleveland Clinic ConsultQD. TEMPO: Tavapadon Shows Promise as Both First and Adjunct Therapy in Parkinson’s. 2025.

5. Practical Neurology. For People with Parkinson Disease, Tavapadon Adjunctive Therapy to Levodopa Increased Good ON Time. AAN 2025.

6. HMP Global Learning Network. Tavapadon Improves Parkinson Disease Motor Fluctuations in Phase 3 Trial. 2026.

7. Cerevel Therapeutics. Tavapadon (CVL-751) Investigator’s Brochure. Version 8.0. 2024.

8. Simuni T, Biglan K, Kurlan R, et al. Rationale and Development of Tavapadon, a D1/D5-Selective Partial Dopamine Agonist for the Treatment of Parkinson’s Disease. J Parkinsons Dis. 2023.

9. Gray D, Satti P, Dhall R, et al. Receptor Binding Profile of Tavapadon (CVL-751): Selectivity for D1/D5 Dopamine Receptors. Mol Pharmacol. 2023.

10. Hrench D, Poewe W, Gilman N, et al. Impulse Control Disorders in Parkinson’s Disease: A Review of Clinical Features, Pathophysiology, and Management. Neurology. 2021.

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13. Olanow CW, Stocchi F. Levodopa: A New Look at an Old Friend. Lancet Neurol. 2018.

14. Movement Disorder Society Task Force on Rating Scales for Parkinson’s Disease. The MDS-UPDRS: Explanation and Elaboration. Mov Disord. 2008.

15. Kurlan R. Parkinson’s Disease: Update on Diagnosis and Management. Neurology. 2024.

16. Hamani C, Fontaine P, Hutchison WD. Motor Circuit Changes in Parkinson’s Disease. Prog Neurol. 2022.

17. Albin RL, Young AB, Penney JB. The Functional Anatomy of Basal Ganglia Disorders. Trends Neurosci. 1989.

18. Parent A, Hazrati LN. Functional Anatomy of the Basal Ganglia. I. The Cortico-Subcortical Loops. Brain Res Rev. 1995.

19. Haber SN. The Place of Dopamine in the Cortico-Basal Ganglia-Thalamic Circuit. Neuropsychopharmacology. 2023.

20. Joutsa J, Johansson J, Al-Faisal W, et al. Ventral Striatal D3 Receptor Availability Predicts Impulsive Behavior in Healthy Humans. Biol Psychiatry. 2022.

Comprehensive Expert Review — IMBR Mentor
For Neurology Board Examination Preparation and Clinical Reference
Last Updated: March 2026
Peer Review Status: Expert-Curated Summary of Publicly Available Trial Data