Targeting the tamoxifen receptor within sodium channels to block osteoarthritic pain Article Swipe
Megan M. McCollum
,
Megan Larmore
,
Shingo Ishihara
,
Leo Ng
,
Louise F. Kimura
,
Eduardo Guadarrama
,
My C. Ta
,
Thuy N. Vien
,
Grant B. Frost
,
Karl A. Scheidt
,
Rachel E. Miller
,
Paul G. DeCaen
·
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.1016/j.celrep.2022.111248
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.1016/j.celrep.2022.111248
Voltage-gated sodium channels (NaV) in nociceptive neurons initiate action potentials required for transmission of aberrant painful stimuli observed in osteoarthritis (OA). Targeting NaV subtypes with drugs to produce analgesic effects for OA pain management is a developing therapeutic area. Previously, we determined the receptor site for the tamoxifen analog N-desmethyltamoxifen (ND-Tam) within a prokaryotic NaV. Here, we report the pharmacology of ND-Tam against eukaryotic NaVs natively expressed in nociceptive neurons. ND-Tam and analogs occupy two conserved intracellular receptor sites in domains II and IV of NaV1.7 to block ion entry using a "bind and plug" mechanism. We find that ND-Tam inhibition of the sodium current is state dependent, conferring a potent frequency- and voltage-dependent block of hyperexcitable nociceptive neuron action potentials implicated in OA pain. When evaluated using a mouse OA pain model, ND-Tam has long-lasting efficacy, which supports the potential of repurposing ND-Tam analogs as NaV antagonists for OA pain management.
Related Topics
Concepts
Tamoxifen
Block (permutation group theory)
Osteoarthritis
Sodium channel
Receptor
Selective estrogen receptor modulator
Sodium
Medicine
Internal medicine
Chemistry
Pharmacology
Bioinformatics
Biology
Breast cancer
Cancer
Pathology
Organic chemistry
Mathematics
Geometry
Alternative medicine
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1016/j.celrep.2022.111248
- http://www.cell.com/article/S221112472201066X/pdf
- OA Status
- gold
- Cited By
- 4
- References
- 69
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4292755761
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4292755761Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1016/j.celrep.2022.111248Digital Object Identifier
- Title
-
Targeting the tamoxifen receptor within sodium channels to block osteoarthritic painWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2022Year of publication
- Publication date
-
2022-08-01Full publication date if available
- Authors
-
Megan M. McCollum, Megan Larmore, Shingo Ishihara, Leo Ng, Louise F. Kimura, Eduardo Guadarrama, My C. Ta, Thuy N. Vien, Grant B. Frost, Karl A. Scheidt, Rachel E. Miller, Paul G. DeCaenList of authors in order
- Landing page
-
https://doi.org/10.1016/j.celrep.2022.111248Publisher landing page
- PDF URL
-
https://www.cell.com/article/S221112472201066X/pdfDirect link to full text PDF
- Open access
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YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
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https://www.cell.com/article/S221112472201066X/pdfDirect OA link when available
- Concepts
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Tamoxifen, Block (permutation group theory), Osteoarthritis, Sodium channel, Receptor, Selective estrogen receptor modulator, Sodium, Medicine, Internal medicine, Chemistry, Pharmacology, Bioinformatics, Biology, Breast cancer, Cancer, Pathology, Organic chemistry, Mathematics, Geometry, Alternative medicineTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
4Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 2, 2024: 1, 2023: 1Per-year citation counts (last 5 years)
- References (count)
-
69Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.mechanism. | 95 |
| abstract_inverted_index.potentials | 9, 120 |
| abstract_inverted_index.Previously, | 39 |
| abstract_inverted_index.antagonists | 147 |
| abstract_inverted_index.management. | 151 |
| abstract_inverted_index.nociceptive | 5, 68, 117 |
| abstract_inverted_index.prokaryotic | 53 |
| abstract_inverted_index.repurposing | 142 |
| abstract_inverted_index.therapeutic | 37 |
| abstract_inverted_index.long-lasting | 135 |
| abstract_inverted_index.pharmacology | 59 |
| abstract_inverted_index.transmission | 12 |
| abstract_inverted_index.Voltage-gated | 0 |
| abstract_inverted_index.intracellular | 76 |
| abstract_inverted_index.Na<sub>V</sub> | 22, 146 |
| abstract_inverted_index.hyperexcitable | 116 |
| abstract_inverted_index.osteoarthritis | 19 |
| abstract_inverted_index.Na<sub>V</sub>. | 54 |
| abstract_inverted_index.Na<sub>V</sub>s | 64 |
| abstract_inverted_index.(Na<sub>V</sub>) | 3 |
| abstract_inverted_index.Na<sub>V</sub>1.7 | 85 |
| abstract_inverted_index.voltage-dependent | 113 |
| abstract_inverted_index.N-desmethyltamoxifen | 49 |
| cited_by_percentile_year.max | 97 |
| cited_by_percentile_year.min | 89 |
| corresponding_author_ids | https://openalex.org/A5026067446 |
| countries_distinct_count | 1 |
| institutions_distinct_count | 12 |
| corresponding_institution_ids | https://openalex.org/I111979921 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/3 |
| sustainable_development_goals[0].score | 0.6800000071525574 |
| sustainable_development_goals[0].display_name | Good health and well-being |
| citation_normalized_percentile.value | 0.71141395 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | False |