ArticleThe Journal of pharmacology and experimental therapeutics2012
Small molecule positive allosteric modulation of TRPV1 activation by vanilloids and acidic pH.
Article in The Journal of pharmacology and experimental therapeutics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.
- A systematic review of the association between immunogenomic markers and cancer-related fatigue.Brain, behavior, and immunity · 2012Pooled it
- Molecular target for neuroinflammation and pain management: transient receptor potential vanilloid 1.Inflammopharmacology · 2026Review
- Review
- Intraarticular resiniferatoxin, a potent TRPV1 agonist, for treatment of osteoarthritic pain.Pain management · 2025Review
- Glutamate stress in the caudal nucleus tractus solitarii (nTS): Impact on respiratory function and synaptic signaling in an Alzheimer's disease model.Experimental neurology · 2025Article
- Article
- Structure-guided peptide engineering of a positive allosteric modulator targeting the outer pore of TRPV1 for long-lasting analgesia.Nature communications · 2023Article
- TRPV1: A promising therapeutic target for skin aging and inflammatory skin diseases.Frontiers in pharmacology · 2023Review
- Transient receptor potential channel involvement in antinociceptive effect of citral in orofacial acute and chronic pain models.EXCLI journal · 2022Article
- De Novo Design of Peptidic Positive Allosteric Modulators Targeting TRPV1 with Analgesic Effects.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Article
- Article
- Effect of 158 herbal remedies on human TRPV1 and the two-pore domain potassium channels KCNK2, 3 and 9.Journal of traditional and complementary medicine · 2020Article
- A centipede toxin causes rapid desensitization of nociceptor TRPV1 ion channel.Toxicon : official journal of the International Society on Toxinology · 2020Article
- Calcium signals that determine vascular resistance.Wiley interdisciplinary reviews. Systems biology and medicine · 2019Review
- Bi-directional modulation of food habit expression by the endocannabinoid system.The European journal of neuroscience · 2019Article
- Understanding diverse TRPV1 signaling - an update.F1000Research · 2019Review
- TRPV1 antagonists that cause hypothermia, instead of hyperthermia, in rodents: Compounds' pharmacological profiles, in vivo targets, thermoeffectors recruited and implications for drug development.Acta physiologica (Oxford, England) · 2018Article
- Pain control through selective chemo-axotomy of centrally projecting TRPV1+ sensory neurons.The Journal of clinical investigation · 2018Article
- Article
- Investigating the involvement of TRPVNaunyn-Schmiedeberg's archives of pharmacology · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
Transient receptor potential cation channel subfamily V member 1 (TRPV1) is a high-conductance, nonselective cation channel strongly expressed in nociceptive primary afferent neurons of the peripheral nervous system and functions as a multimodal nociceptor gated by temperatures greater than 43°C, protons, and small-molecule vanilloid ligands such as capsaicin. The ability to respond to heat, low pH, vanilloids, and endovanilloids and altered sensitivity and expression in experimental inflammatory and neuropathic pain models made TRPV1 a major target for the development of novel, nonopioid analgesics and resulted in the discovery of potent antagonists. In human clinical trials, observations of hyperthermia and the potential for thermal damage by suppressing the ability to sense noxious heat suggested that full-scale blockade of TRPV1 function can be counterproductive and subtler pharmacological approaches are necessary. Here we show that the dihydropyridine derivative 4,5-diethyl-3-(2-methoxyethylthio)-2-methyl-6-phenyl-1,4-(±)-dihydropyridine-3,5-dicarboxylate (MRS1477) behaves as a positive allosteric modulator of both proton and vanilloid activation of TRPV1. Under inflammatory-mimetic conditions of low pH (6.0) and protein kinase C phosphorylation, addition of MRS1477 further increased sensitivity of already sensitized TPRV1 toward capsaicin. MRS1477 does not affect inhibition by capsazepine or ruthenium red and remains effective in potentiating activation by pH in the presence of an orthosteric vanilloid antagonist. These results indicate a distinct site on TRPV1 for positive allosteric modulation that may bind endogenous compounds or novel pharmacological agents. Positive modulation of TRPV1 sensitivity suggests that it may be possible to produce a selective analgesia through calcium overload restricted to highly active nociceptive nerve endings at sites of tissue damage and inflammation.
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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.