ArticleChannels (Austin, Tex.)2022
Association of respiratory failure with inhibition of NaV1.6 in the phrenic nerve.
Article in Channels (Austin, Tex.), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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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.
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Who cites it
4 citing papers in PubMed, 4 citations in OpenAlex.
- Effects of Tetrodotoxin on Safety, and Sensory and Respiratory Systems: A Dose-Escalating Study in Healthy Volunteers.European journal of pain (London, England) · 2026Article
- Voltage-gated sodium channels in excitable cells as drug targets.Nature reviews. Drug discovery · 2025Review
- Post-procedure sedation and apnea linked to ion channel variant: a case report on dexmedetomidine-propofol interaction.Frontiers in pharmacology · 2025Article
- Discovery of Arylsulfonamide NaACS medicinal chemistry letters · 2021Article
Corrections and comments
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Authors and funding
22 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
As part of a drug discovery effort to identify potent inhibitors of NaV1.7 for the treatment of pain, we observed that inhibitors produced unexpected cardiovascular and respiratory effects in vivo. Specifically, inhibitors administered to rodents produced changes in cardiovascular parameters and respiratory cessation. We sought to determine the mechanism of the in vivo adverse effects by studying the selectivity of the compounds on NaV1.5, NaV1.4, and NaV1.6 in in vitro and ex vivo assays. Inhibitors lacking sufficient NaV1.7 selectivity over NaV1.6 were associated with respiratory cessation after in vivo administration to rodents. Effects on respiratory rate in rats were consistent with effects in an ex vivo hemisected rat diaphragm model and in vitro NaV1.6 potency. Furthermore, direct blockade of the phrenic nerve signaling was observed at exposures known to cause respiratory cessation in rats. Collectively, these results support a significant role for NaV1.6 in phrenic nerve signaling and respiratory function.
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