ArticleBritish journal of pharmacology2015
A novel selective and orally bioavailable Nav 1.8 channel blocker, PF-01247324, attenuates nociception and sensory neuron excitability.
Article in British journal of pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 1 of them a synthesis that pooled it.
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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
62 citing papers in PubMed, 1 synthesis or guideline pooled it, 97 citations in OpenAlex.
- Comparative Efficacy and Safety of 11 Drugs as Therapies for Adults With Neuropathic Pain After Spinal Cord Injury: A Bayesian Network Analysis Based on 20 Randomized Controlled Trials.Frontiers in neurology · 2022Pooled it
- A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Crossover Study to Evaluate the Pharmacodynamic Effects of VX-150, a Highly Selective NaV1.8 Inhibitor, in Healthy Male Adults.Pain medicine (Malden, Mass.) · 2021Trial
- Chasing the Wrong Door for 30 Years: Is Suzetrigine the Key to Selective Pain Relief?Medicina (Kaunas, Lithuania) · 2026Review
- Ion-Channel Activity of Characteristic Alkaloids From Uncaria rhynchophylla.Chemistry & biodiversity · 2026Article
- Functional role of Nav1.8 channels in action potentials of mouse CGRP-lineage dorsal root ganglion neurons.The Journal of physiology · 2026Article
- Selective NaV1.8 Inhibition for Pain Management: Current Evidence and Future Potential of Suzetrigine.Current pain and headache reports · 2026Review
- Shaping the Action Potential in Dorsal Root and Trigeminal Ganglia Neurons: Relevance to Pain Mechanisms.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Review
- Suzetrigine, a NaMolecules (Basel, Switzerland) · 2026Review
- Targeting sodium channels - challenges for acute pain and the leap to chronic pain.Nature reviews. Neurology · 2025Review
- Modulation of human dorsal root ganglion neuron firing by the Nav1.8 inhibitor suzetrigine.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Nav1.8 and Chronic Pain: From Laboratory Animals to Clinical Patients.Biomolecules · 2025Review
- Voltage-gated sodium channels in excitable cells as drug targets.Nature reviews. Drug discovery · 2025Review
- Human sensory neurons exhibit cell-type-specific, pain-associated differences in intrinsic excitability and expression ofbioRxiv : the preprint server for biology · 2025Article
- Sodium channels as a new target for pain treatment.Frontiers in pharmacology · 2025Review
- Discovery of E0199: A novel compound targeting both peripheral NaJournal of pharmaceutical analysis · 2025Article
- State-Dependent Inhibition of Nav1.8 Sodium Channels by VX-150 and VX-548.Molecular pharmacology · 2024Article
- Article
- Directions for analgesic development.Journal of anesthesia and translational medicine · 2024Review
- Nanomedicine and voltage-gated sodium channel blockers in pain management: a game changer or a lost cause?Drug delivery and translational research · 2024Review
- NaInternational journal of molecular sciences · 2024Article
2 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
24 authors at 4 institutions in 2 countries.
Funding
Abstract
background and purposeNaV 1.8 ion channels have been highlighted as important molecular targets for the design of low MW blockers for the treatment of chronic pain. Here, we describe the effects of PF-01247324, a new generation, selective, orally bioavailable Nav 1.8 channel blocker of novel chemotype. EXPERIMENTAL APPROACH: The inhibition of Nav 1.8 channels by PF-01247324 was studied using in vitro patch-clamp electrophysiology and the oral bioavailability and antinociceptive effects demonstrated using in vivo rodent models of inflammatory and neuropathic pain. KEY
resultsPF-01247324 inhibited native tetrodotoxin-resistant (TTX-R) currents in human dorsal root ganglion (DRG) neurons (IC50 : 331 nM) and in recombinantly expressed h Nav 1.8 channels (IC50 : 196 nM), with 50-fold selectivity over recombinantly expressed TTX-R hNav 1.5 channels (IC50 : ∼10 μM) and 65-100-fold selectivity over TTX-sensitive (TTX-S) channels (IC50 : ∼10-18 μM). Native TTX-R currents in small-diameter rodent DRG neurons were inhibited with an IC50 448 nM, and the block of both human recombinant Nav 1.8 channels and TTX-R from rat DRG neurons was both frequency and state dependent. In vitro current clamp showed that PF-01247324 reduced excitability in both rat and human DRG neurons and also altered the waveform of the action potential. In vivo experiments n rodents demonstrated efficacy in both inflammatory and neuropathic pain models. CONCLUSIONS AND IMPLICATIONS: Using PF-01247324, we have confirmed a role for Nav 1.8 channels in both inflammatory and neuropathic pain. We have also demonstrated a key role for Nav 1.8 channels in action potential upstroke and repetitive firing of rat and human DRG neurons.
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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.