Trial reportClinical pharmacology in drug development2021
Safety, Tolerability, and Pharmacokinetics of Mevidalen (LY3154207), a Centrally Acting Dopamine D1 Receptor-Positive Allosteric Modulator (D1PAM), in Healthy Subjects.
Trial report in Clinical pharmacology in drug development, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 17 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Multiple-Ascending Dose, Safety, Tolerability, and Pharmacokinetic Study of LY3154207 in Healthy Subjects and Subjects With Parkinson's Disease
Disposition of [14C]-LY3154207 Following Oral Administration in Healthy Male Subjects
Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.
- The Signaling and Pharmacology of the Dopamine D1 Receptor.Frontiers in cellular neuroscience · 2021Pooled it
- Safety and Efficacy of Mevidalen in Lewy Body Dementia: A Phase 2, Randomized, Placebo-Controlled Trial.Movement disorders : official journal of the Movement Disorder Society · 2022Trial
- Cardiovascular pharmacology of dopaminergic agents in humans: a review.Clinical autonomic research : official journal of the Clinical Autonomic Research Society · 2026Review
- Elucidating biased signaling in class A GPCRs.Trends in pharmacological sciences · 2025Review
- Functional dynamics of G protein-coupled receptors reveal new routes for drug discovery.Nature reviews. Drug discovery · 2025Review
- Lewy Body Dementia: An Overview of Promising Therapeutics.Current neurology and neuroscience reports · 2023Review
- The Molecular Mechanism of Positive Allosteric Modulation at the Dopamine D1 Receptor.International journal of molecular sciences · 2023Article
- The molecular mechanism of positive allosteric modulation at the dopamine D1 receptor.bioRxiv : the preprint server for biology · 2023Article
- Effects of DPTQ, a novel positive allosteric modulator of the dopamine D1 receptor, on spontaneous eye blink rate and spatial working memory in the nonhuman primate.Psychopharmacology · 2023Article
- Progress and Pitfalls in Developing Agents to Treat Neurocognitive Deficits Associated with Schizophrenia.CNS drugs · 2022Review
- Ligand recognition and biased agonism of the D1 dopamine receptor.Nature communications · 2022Article
- Safety, Tolerability, and Pharmacokinetics of Mevidalen (LY3154207), a Centrally Acting Dopamine D1 Receptor-Positive Allosteric Modulator, in Patients With Parkinson Disease.Clinical pharmacology in drug development · 2022Article
- Dopamine D1R Receptor Stimulation as a Mechanistic Pro-cognitive Target for Schizophrenia.Schizophrenia bulletin · 2022Article
- Evaluating the Use of Digital Biomarkers to Test Treatment Effects on Cognition and Movement in Patients with Lewy Body Dementia.Journal of Parkinson's disease · 2022Article
- Cognitive Deficit in Schizophrenia: From Etiology to Novel Treatments.International journal of molecular sciences · 2021Review
- Enantioenriched Positive Allosteric Modulators Display Distinct Pharmacology at the Dopamine DMolecules (Basel, Switzerland) · 2021Article
- Using Clinical Scales and Digital Measures to Explore Falls in Patients with Lewy Body Dementia.Digital biomarkersArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activation of the brain dopamine D1 receptor has attracted attention because of its promising role in neuropsychiatric diseases. Although efforts to develop D1 agonists have been challenging, a positive allosteric modulator (PAM), represents an attractive approach with potential better drug-like properties. Phase 1 single-ascending-dose (SAD; NCT03616795) and multiple-ascending-dose (MAD; NCT02562768) studies with the D1PAM mevidalen (LY3154207) were conducted with healthy subjects. There were no treatment-related serious adverse events (AEs) in these studies. In the SAD study, 25-200 mg administered orally showed dose-proportional pharmacokinetics (PK) and acute dose-related increases in systolic blood pressure (SBP) and diastolic blood pressure DBP) and pulse rate at doses ≥ 75 mg. AE related to central activation were seen at doses ≥ 75 mg. At 25 and 75 mg, central penetration of mevidalen was confirmed by measurement of mevidalen in cerebrospinal fluid. In the MAD study, once-daily doses of mevidalen at 15-150 mg for 14 days showed dose-proportional PK. Acute dose-dependent increases in SBP, DBP, and PR were observed on initial administration, but with repeated dosing the effects diminished and returned toward baseline levels. Overall, these findings support further investigation of mevidalen as a potential treatment for a range of neuropsychiatric disorders.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.