ArticleNaunyn-Schmiedeberg's archives of pharmacology2015
AMG2850, a potent and selective TRPM8 antagonist, is not effective in rat models of inflammatory mechanical hypersensitivity and neuropathic tactile allodynia.
Article in Naunyn-Schmiedeberg's archives of pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- Mechanosensitive receptors in migraine: a systematic review.The journal of headache and pain · 2024Pooled it
- Molecular basis for cold and menthol sensing by mammalian TRPM8.Nature communications · 2026Article
- Cold- and TRPM8-dependent shaking in mammals and birds.Communications biology · 2025Article
- A mosquito proboscis-inspired cambered microneedle patch for ophthalmic regional anaesthesia.Journal of advanced research · 2025Article
- Mechanisms of sensory adaptation and inhibition of the cold and menthol receptor TRPM8.Science advances · 2024Article
- β-Lactam TRPM8 Antagonist RGM8-51 Displays Antinociceptive Activity in Different Animal Models.International journal of molecular sciences · 2022Article
- Transient Receptor Potential (TRP) Ion Channels Involved in Malignant Glioma Cell Death and Therapeutic Perspectives.Frontiers in cell and developmental biology · 2021Review
- Recent Progress in TRPM8 Modulation: An Update.International journal of molecular sciences · 2019Review
- Antinociceptive effect of two novel transient receptor potential melastatin 8 antagonists in acute and chronic pain models in rat.British journal of pharmacology · 2018Article
- Regulation of Pain and Itch by TRP Channels.Neuroscience bulletin · 2018Review
- Article
- Development of TRPM8 Antagonists to Treat Chronic Pain and Migraine.Pharmaceuticals (Basel, Switzerland) · 2017Review
- TRPM8 and Migraine.Headache · 2016Review
- TRPM8: a potential target for cancer treatment.Journal of cancer research and clinical oncology · 2016Review
- Article
- Molecular Targets of Cannabidiol in Neurological Disorders.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2015Review
- Targeting TRP channels: beyond TRPV1.Naunyn-Schmiedeberg's archives of pharmacology · 2015Article
- Review
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
TRPM8 has been implicated in pain and migraine based on dorsal root- and trigeminal ganglion-enriched expression, upregulation in preclinical models of pain, knockout mouse studies, and human genetics. Here, we evaluated the therapeutic potential in pain of AMG2850 ((R)-8-(4-(trifluoromethyl)phenyl)-N-((S)-1,1,1-trifluoropropan-2-yl)-5,6-dihydro-1,7-naphthyridine-7(8H)-carboxamide), a small molecule antagonist of TRPM8 by in vitro and in vivo characterization. AMG2850 is potent in vitro at rat TRPM8 (IC90 against icilin activation of 204 ± 28 nM), highly selective (>100-fold IC90 over TRPV1 and TRPA1 channels), and orally bioavailable (F po > 40 %). When tested in a skin-nerve preparation, AMG2850 blocked menthol-induced action potentials but not mechanical activation in C fibers. AMG2850 exhibited significant target coverage in vivo in a TRPM8-mediated icilin-induced wet-dog shake (WDS) model in rats (at 10 mg/kg p.o.). However, AMG2850 did not produce a significant therapeutic effect in rat models of inflammatory mechanical hypersensitivity or neuropathic tactile allodynia at doses up to 100 mg/kg. The lack of efficacy suggests that either TRPM8 does not play a role in mediating pain in these models or that a higher level of target coverage is required. The potential of TRPM8 antagonists as migraine therapeutics is yet to be determined.
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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.