ArticleActa physiologica (Oxford, England)2018
TRPV1 antagonists that cause hypothermia, instead of hyperthermia, in rodents: Compounds' pharmacological profiles, in vivo targets, thermoeffectors recruited and implications for drug development.
Article in Acta physiologica (Oxford, England), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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38 citing papers in PubMed, 1 synthesis or guideline pooled it, 87 citations in OpenAlex.
- Menthol can be safely applied to improve thermal perception during physical exercise: a meta-analysis of randomized controlled trials.Scientific reports · 2020Pooled it
- Motugivatrep (SJP-0132) 0.3% Ophthalmic Suspension for Dry Eye Disease: A Randomized, Double-Masked, Placebo-Controlled, Multicenter, Phase 3 Trial.Clinical ophthalmology (Auckland, N.Z.) · 2026Trial
- Current and Developing Therapeutics for Dry Eye Disease: Targeting Ion Channels.Current issues in molecular biology · 2026Review
- Modulation of ion channels as emerging therapeutic targets in the treatment of diabetic neuropathy.EXCLI journal · 2026Review
- Physiological functions and pharmacological targeting of transient receptor potential channels.Pharmacological reviews · 2025Review
- Insights into ion channels to identify drug target for neuropathic pain management.Inflammopharmacology · 2025Review
- Effects of Hydrogen Sulfide at Normal Body Temperature and in the Cold on Isolated Tail and Carotid Arteries from Rats and TRPA1 Knockout and Wild-Type Mice.Biomedicines · 2024Article
- The Endocannabinoid Peptide RVD-Hemopressin Is a TRPV1 Channel Blocker.Biomolecules · 2024Article
- Discovery and Profiling of New Multimodal Phenylglycinamide Derivatives as Potent Antiseizure and Antinociceptive Drug Candidates.ACS chemical neuroscience · 2024Article
- GLP-1 and Its Derived Peptides Mediate Pain Relief Through Direct TRPV1 Inhibition Without Affecting Thermoregulation.Research square · 2024Article
- Recent Advances in Computer-Aided Structure-Based Drug Design on Ion Channels.International journal of molecular sciences · 2023Review
- A human TRPV1 genetic variant within the channel gating domain regulates pain sensitivity in rodents.The Journal of clinical investigation · 2023Article
- Natural Active Ingredients and TRPV1 Modulation: Focus on Key Chemical Moieties Involved in Ligand-Target Interaction.Plants (Basel, Switzerland) · 2023Review
- The neural pathway of the hyperthermic response to antagonists of the transient receptor potential vanilloid-1 channel.Temperature (Austin, Tex.) · 2023Article
- Progress in the Structural Basis of thermoTRP Channel Polymodal Gating.International journal of molecular sciences · 2023Review
- Diosgenin Exerts Analgesic Effects by Antagonizing the Selective Inhibition of Transient Receptor Potential Vanilloid 1 in a Mouse Model of Neuropathic Pain.International journal of molecular sciences · 2022Article
- Article
- Venom Peptide Toxins Targeting the Outer Pore Region of Transient Receptor Potential Vanilloid 1 in Pain: Implications for Analgesic Drug Development.International journal of molecular sciences · 2022Review
- Anatomical Analysis of Transient Potential Vanilloid Receptor 1 (Frontiers in molecular neuroscience · 2022Article
- Advances in TRP channel drug discovery: from target validation to clinical studies.Nature reviews. Drug discovery · 2022Review
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimThermoregulatory side effects hinder the development of transient receptor potential vanilloid-1 (TRPV1) antagonists as new painkillers. While many antagonists cause hyperthermia, a well-studied effect, some cause hypothermia. The mechanisms of this hypothermia are unknown and were studied herein.
methodsTwo hypothermia-inducing TRPV1 antagonists, the newly synthesized A-1165901 and the known AMG7905, were used in physiological experiments in rats and mice. Their pharmacological profiles against rat TRPV1 were studied in vitro.
resultsAdministered peripherally, A-1165901 caused hypothermia in rats by either triggering tail-skin vasodilation (at thermoneutrality) or inhibiting thermogenesis (in the cold). A-1165901-induced hypothermia did not occur in rats with desensitized (by an intraperitoneal dose of the TRPV1 agonist resiniferatoxin) sensory abdominal nerves. The hypothermic responses to A-1165901 and AMG7905 (administered intragastrically or intraperitoneally) were absent in Trpv1
conclusionTRPV1 antagonists cause hypothermia by an on-target action: on TRPV1 channels on abdominal sensory nerves. These channels are tonically activated by protons and drive the reflectory inhibition of thermogenesis and tail-skin vasoconstriction. Those TRPV1 antagonists that cause hypothermia further inhibit these cold defences, thus decreasing body temperature. SIGNIFICANCE: TRPV1 antagonists (of capsaicin activation) are highly unusual in that they can cause both hyper- and hypothermia by modulating the same mechanism. For drug development, this means that both side effects can be dealt with simultaneously, by minimizing these compounds' interference with TRPV1 activation by protons.
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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.