ArticlePain2017
Primidone inhibits TRPM3 and attenuates thermal nociception in vivo.
Article in Pain, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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.
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Who cites it
50 citing papers in PubMed, 106 citations in OpenAlex.
- Stereoselectivity and functional plasticity of a common ligand-binding pocket in TRPM3.Nature communications · 2026Article
- TRPM3 mediates spontaneous pain and mechanical allodynia in a mouse model of chronic orofacial neuropathy.Cell reports. Medicine · 2026Article
- Osteoarthritis: molecular pathogenesis and potential therapeutic options.Signal transduction and targeted therapy · 2026Review
- A duo of redox-sensitive pore-loop cysteines controls the activity of the neural ion channel TRPM3.Communications chemistry · 2026Article
- Structural basis for agonist and heat activation of nociceptor TRPM3.Nature structural & molecular biology · 2026Article
- Physiological functions and pharmacological targeting of transient receptor potential channels.Pharmacological reviews · 2025Review
- Muscarinic Receptor Antagonism and TRPM3 Activation as Stimulators of Mitochondrial Function and Axonal Repair in Diabetic Sensorimotor Polyneuropathy.International journal of molecular sciences · 2025Review
- Functional Upregulation of TRPM3 Channels Contributes to Acute Pancreatitis-associated Pain and Inflammation.Inflammation · 2025Article
- Molecular basis of neurosteroid and anticonvulsant regulation of TRPM3.Nature structural & molecular biology · 2025Article
- Stimulus-Transcription Coupling of TRPM3 Channels: A Signaling Pathway from the Plasma Membrane to the Nucleus.Biomolecules · 2025Review
- Phenotype Spectrum of TRPM3-Associated Disorders.Annals of neurology · 2025Article
- Sex difference in TRPM3 channel functioning in nociceptive and vascular systems: an emerging target for migraine therapy in females?The journal of headache and pain · 2025Review
- Targeting TRPM3 as a potential therapeutic approach for autosomal dominant polycystic kidney disease.Scientific reports · 2025Article
- TRP channels in epileptogenesis: calcium dysregulation mechanisms and pharmacological targeting strategies.Frontiers in molecular neuroscience · 2025Review
- Inhibition of TRPM3 by Primidone Provides a Potential Therapeutic Method for Adenomyosis Management.Drug design, development and therapy · 2025Article
- Anesthetic- and Analgesic-Related Drugs Modulating Both Voltage-Gated NaBiomolecules · 2024Review
- Navigating the Controversies: Role of TRPM Channels in Pain States.International journal of molecular sciences · 2024Review
- TRPM3, TRPM4, and TRPM5 as thermo-sensitive channels.The journal of physiological sciences : JPS · 2024Review
- A Cataract-Causing Mutation in the TRPM3 Cation Channel Disrupts Calcium Dynamics in the Lens.Cells · 2024Article
- Case Report: Expanded delineation of phenotype of TRPM3-related neurodevelopmental disorders.Frontiers in pediatrics · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The melastatin-related transient receptor potential (TRP) channel TRPM3 is a nonselective cation channel expressed in nociceptive neurons and activated by heat. Because TRPM3-deficient mice show inflammatory thermal hyperalgesia, pharmacological inhibition of TRPM3 may exert antinociceptive properties. Fluorometric Ca influx assays and a compound library containing approved or clinically tested drugs were used to identify TRPM3 inhibitors. Biophysical properties of channel inhibition were assessed using electrophysiological methods. The nonsteroidal anti-inflammatory drug diclofenac, the tetracyclic antidepressant maprotiline, and the anticonvulsant primidone were identified as highly efficient TRPM3 blockers with half-maximal inhibition at 0.6 to 6 μM and marked specificity for TRPM3. Most prominently, primidone was biologically active to suppress TRPM3 activation by pregnenolone sulfate (PregS) and heat at concentrations markedly lower than plasma concentrations commonly used in antiepileptic therapy. Primidone blocked PregS-induced Cai influx through TRPM3 by allosteric modulation and reversibly inhibited atypical inwardly rectifying TRPM3 currents induced by coapplication of PregS and clotrimazole. In vivo, analgesic effects of low doses of primidone were demonstrated in mice, applying PregS- and heat-induced pain models, including inflammatory hyperalgesia. Thus, applying the approved drug at concentrations that are lower than those needed to induce anticonvulsive effects offers a shortcut for studying physiological and pathophysiological roles of TRPM3 in vivo.
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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.