Component

Capsazepine

Experimental TRPV1 antagonist; pharmacological probe.

5 recorded relationships. Experimental role, claim status and evidence remain attached to each record.

Read recorded mechanisms Open recursive mind map

How nutrients influence it

Every nutrient with a recorded effect on this component, credited to the nutrient that acted rather than the chapter that recorded it. Open a nutrient to see the findings and the conditions they were measured under.

How nutrients reach it in more than one step

Chains of two or more recorded steps that end here, grouped by the nutrient they start from. Each step is a separate finding, so a chain is a route a mechanism could take, not proof that it does.

Tracing routes…

What it does

Every recorded relationship this component is part of, grouped by its role. Plain wording comes first; the technical statement follows.

Recorded relationships

What it acts on

  1. Capsazepine inhibited the gamma-nonalactone-evoked TRPV1 calcium response.

    Capsazepine → Calcium response of human-TRPV1-expressing HEK293 cells source_derived_draftungraded
    Experimental context and source evidence
    dose
    Gamma-nonalactone 2 mM; capsazepine 1 micromolar or A-967079 1 micromolar
    duration
    Acute fluorescence assay
    evidence_access
    Primary full-text methods/results inspected; PubMed metadata where indexed.
    evidence_scope
    literature_reviewed; model-specific source-derived curation
    experimental_model
    Human TRPV1 or TRPA1 expressed in HEK293 cells
    limitations
    Pharmacological specificity controls support channel involvement; they do not establish a binding pocket or oral therapeutic exposure.
    nutrient_topic
    Gamma-nonalactone flavor-compound chapter; nutrient and drug interactions retain their experimental settings. · Gamma-nonalactone
    organism
    Human TRPV1 or TRPA1 expressed in HEK293 cells
    plain_language
    Capsazepine inhibited the gamma-nonalactone-evoked TRPV1 calcium response.
    primary_references
    Agonistic/antagonistic properties of lactones in food flavors on the sensory ion channels TRPV1 and TRPA1. (2022). https://pubmed.ncbi.nlm.nih.gov/36374622/ DOI: 10.1093/chemse/bjac023
    route
    In vitro co-exposure
    tissue
    Receptor antagonist controls

    Gamma-nonalactone: mechanisms, molecular forms and cross-actor connections (2026-09-20) · lines 70–79

    Original AI-assisted curation of eight primary studies. Study-specific citations, negative findings and limitations retained. Not publisher full text. · supports · Human TRPV1 or TRPA1 expressed in HEK293 cells · source_derived_draft · unverified_draft

    ## gamma-nonalactone-capsazepine-control Capsazepine inhibited the gamma-nonalactone-evoked TRPV1 calcium response. Model/species: Human TRPV1 or TRPA1 expressed in HEK293 cells Tissue: Receptor antagonist controls Exposure: Gamma-nonalactone 2 mM; capsazepine 1 micromolar or A-967079 1 micromolar Route: In vitro co-exposure Duration: Acute fluorescence assay Limits: Pharmacological specificity controls support channel involvement; they do not establish a binding pocket or oral therapeutic exposure. Primary reference: Agonistic/antagonistic properties of lactones in food flavors on the sensory ion channels TRPV1 and TRPA1. (2022). https://pubmed.ncbi.nlm.nih.gov/36374622/ DOI: 10.1093/chemse/bjac023 Access: Primary full-text methods/results inspected; PubMed metadata where indexed.
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. Eugenol inhibited action potentials and both tetrodotoxin-sensitive and resistant sodium currents in rat dental afferent neurons, and capsazepine did not prevent the current inhibition.

    Eugenol → Voltage-gated sodium currents in rat dental afferent neurons source_derived_draftungraded
    Experimental context and source evidence
    dose
    Eugenol concentration-response with capsazepine
    duration
    Acute
    evidence_access
    Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
    evidence_scope
    literature_reviewed; model-specific source-derived curation
    experimental_model
    Retrogradely labeled rat dental primary afferent neurons
    limitations
    The sodium-current effect was TRPV1-independent in this assay; it does not specify a safe human pulp concentration.
    nutrient_topic
    Eugenol chapter; interacting nutrients, drugs, peptides and proteins retain their experimental settings. · Eugenol
    organism
    Retrogradely labeled rat dental primary afferent neurons
    plain_language
    Eugenol inhibited action potentials and both tetrodotoxin-sensitive and resistant sodium currents in rat dental afferent neurons, and capsazepine did not prevent the current inhibition.
    primary_references
    Eugenol inhibits sodium currents in dental afferent neurons. (2006). https://pubmed.ncbi.nlm.nih.gov/16998128/ DOI: 10.1177/154405910608501005
    route
    In vitro
    tissue
    Whole-cell voltage-gated sodium current

    Eugenol: mechanism of action and interactions (2026-09-20) · lines 44–53

    Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. Not publisher full text. · supports · Retrogradely labeled rat dental primary afferent neurons · source_derived_draft · unverified_draft

    ## eugenol-dental-sodium-current Eugenol inhibited action potentials and both tetrodotoxin-sensitive and resistant sodium currents in rat dental afferent neurons, and capsazepine did not prevent the current inhibition. Model/species: Retrogradely labeled rat dental primary afferent neurons Tissue/system: Whole-cell voltage-gated sodium current Exposure: Eugenol concentration-response with capsazepine Route: In vitro Duration: Acute Limits: The sodium-current effect was TRPV1-independent in this assay; it does not specify a safe human pulp concentration. Primary reference: Eugenol inhibits sodium currents in dental afferent neurons. (2006). https://pubmed.ncbi.nlm.nih.gov/16998128/ DOI: 10.1177/154405910608501005 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
    Complete structured claim and evidence

  2. Capsaicin dose-dependently reduced mitochondrial membrane potential in primary cardiomyocytes, and capsazepine or cyclosporine blocked the effect.

    Capsaicin → Cardiomyocyte mitochondrial membrane potential source_derived_draftungraded
    Experimental context and source evidence
    dose
    Capsaicin with capsazepine or cyclosporine controls
    duration
    Acute
    evidence_access
    Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
    evidence_scope
    literature_reviewed; model-specific source-derived curation
    experimental_model
    Primary cardiomyocytes; rat reperfusion model for downstream peptide work
    limitations
    The later infarct-size benefit was produced by the V1-cal peptide, not by capsaicin; capsaicin itself must not inherit that therapeutic result.
    nutrient_topic
    Capsaicin chapter; interacting nutrients, drugs, peptides and proteins retain their experimental settings. · Capsaicin
    organism
    Primary cardiomyocytes; rat reperfusion model for downstream peptide work
    plain_language
    Capsaicin dose-dependently reduced mitochondrial membrane potential in primary cardiomyocytes, and capsazepine or cyclosporine blocked the effect.
    primary_references
    Transient Receptor Potential Vanilloid 1 Regulates Mitochondrial Membrane Potential and Myocardial Reperfusion Injury. (2016). https://pubmed.ncbi.nlm.nih.gov/27671317/ DOI: 10.1161/JAHA.116.003774
    route
    In vitro
    tissue
    Mitochondrial TRPV1 and membrane potential

    Capsaicin: mechanism of action and interactions (2026-09-20) · lines 121–130

    Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. Not publisher full text. · supports · Primary cardiomyocytes; rat reperfusion model for downstream peptide work · source_derived_draft · unverified_draft

    ## capsaicin-cardiomyocyte-mitochondria Capsaicin dose-dependently reduced mitochondrial membrane potential in primary cardiomyocytes, and capsazepine or cyclosporine blocked the effect. Model/species: Primary cardiomyocytes; rat reperfusion model for downstream peptide work Tissue/system: Mitochondrial TRPV1 and membrane potential Exposure: Capsaicin with capsazepine or cyclosporine controls Route: In vitro Duration: Acute Limits: The later infarct-size benefit was produced by the V1-cal peptide, not by capsaicin; capsaicin itself must not inherit that therapeutic result. Primary reference: Transient Receptor Potential Vanilloid 1 Regulates Mitochondrial Membrane Potential and Myocardial Reperfusion Injury. (2016). https://pubmed.ncbi.nlm.nih.gov/27671317/ DOI: 10.1161/JAHA.116.003774 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
    Complete structured claim and evidence

  3. The antinociceptive effect of acetaminophen at an oral dose lacking hypolocomotor activity was absent in fatty acid amide hydrolase and TRPV1 knockout mice in the formalin, tail immersion and von Frey tests, that dose did not affect global brain contents of prostaglandin E2 or endocannabinoids, intracerebroventricular injection of AM404 produced a TRPV1-mediated antinociceptive effect in the formalin test, and pharmacological inhibition of brain TRPV1 by intracerebroventricular capsazepine abolished the antinociceptive effect of oral acetaminophen.

    Human transient receptor potential vanilloid 1 / TRPV1 → Antinociception in thermal, mechanical and chemical pain tests source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_span
    {"source_cache": "artifacts/paracetamol-research/20862299.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2cb3934d80d1a7a6632c49f2007cb6e203b3851706a4ffeb43fda2bb655fa8f2", "start_char": 0, "end_char": 1701, "text_sha256": "2cb3934d80d1a7a6632c49f2007cb6e203b3851706a4ffeb43fda2bb655fa8f2"}
    experimental_model
    Formalin, tail immersion and von Frey tests in fatty acid amide hydrolase and TRPV1 knockout mice with intracerebroventricular injection
    exposure
    Oral acetaminophen at a dose lacking hypolocomotor activity, with intracerebroventricular AM404 and capsazepine
    limitations
    Two separate knockouts and a central antagonist all point the same way, and the dose was chosen to avoid sedation confounding the pain tests. Brain prostaglandin E2 was unchanged at that dose, which is a notable negative.
    nutrient_topic
    Paracetamol research collection; topical membership is not evidence of a direct clinical effect, and the drug is recorded separately from the metabolites NAPQI and AM404. · Paracetamol
    organism
    Mouse
    plain_language
    Remove the channel and the painkiller stops working, while putting the metabolite straight into the brain works.
    primary_references
    [apap-p20862299] TRPV1 in brain is involved in acetaminophen-induced antinociception. (2010). https://pubmed.ncbi.nlm.nih.gov/20862299/ DOI: 10.1371/journal.pone.0012748
    tissue_or_cell_type
    Brain
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Paracetamol: the enzyme it reduces rather than blocks, the isoform that turned out not to exist, the metabolite that carries the analgesia, and the metabolite that destroys the liver (2026-09-22) · lines 311–322

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Formalin, tail immersion and von Frey tests in fatty acid amide hydrolase and TRPV1 knockout mice with intracerebroventricular injection · source_derived_draft · unverified_draft

    ### apap-analgesia-needs-trpv1 The antinociceptive effect of acetaminophen at an oral dose lacking hypolocomotor activity was absent in fatty acid amide hydrolase and TRPV1 knockout mice in the formalin, tail immersion and von Frey tests, that dose did not affect global brain contents of prostaglandin E2 or endocannabinoids, intracerebroventricular injection of AM404 produced a TRPV1-mediated antinociceptive effect in the formalin test, and pharmacological inhibition of brain TRPV1 by intracerebroventricular capsazepine abolished the antinociceptive effect of oral acetaminophen. Condition category: machinery_impairment nutrient_topic: Paracetamol research collection; topical membership is not evidence of a direct clinical effect, and the drug is recorded separately from the metabolites NAPQI and AM404. plain_language: Remove the channel and the painkiller stops working, while putting the metabolite straight into the brain works. organism: Mouse tissue_or_cell_type: Brain experimental_model: Formalin, tail immersion and von Frey tests in fatty acid amide hydrolase and TRPV1 knockout mice with intracerebroventricular injection limitations: Two separate knockouts and a central antagonist all point the same way, and the dose was chosen to avoid sedation confounding the pain tests. Brain prostaglandin E2 was unchanged at that dose, which is a notable negative. exposure: Oral acetaminophen at a dose lacking hypolocomotor activity, with intracerebroventricular AM404 and capsazepine evidence_span: {"source_cache": "artifacts/paracetamol-research/20862299.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2cb3934d80d1a7a6632c49f2007cb6e203b3851706a4ffeb43fda2bb655fa8f2", "start_char": 0, "end_char": 1701, "text_sha256": "2cb3934d80d1a7a6632c49f2007cb6e203b3851706a4ffeb43fda2bb655fa8f2"} [apap-p20862299] TRPV1 in brain is involved in acetaminophen-induced antinociception. (2010). https://pubmed.ncbi.nlm.nih.gov/20862299/ DOI: 10.1371/journal.pone.0012748
    Complete structured claim and evidence

  4. Capsaicin reversibly and concentration-dependently reduced the peak amplitude of the compound action potential, the TRPV1 antagonist capsazepine did not affect this activity, and the powerful TRPV1 agonist resiniferatoxin had no effect on compound action potentials, indicating no involvement of TRPV1 channels; capsaicin analogs and other vanilloids inhibited them in the same concentration-dependent way.

    Dihydrocapsaicin → Fast-conducting compound action potential in peripheral nerve source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/dihydrocapsaicin-research/23352977.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8a2b1f1a1bde0cfc3d08340f1951d88fb3711df6a40634a8c4c7bac63f8384bb", "start_char": 0, "end_char": 1707, "text_sha256": "8a2b1f1a1bde0cfc3d08340f1951d88fb3711df6a40634a8c4c7bac63f8384bb"}
    experimental_model
    Compound action potentials recorded from frog sciatic nerve fibres by the air-gap method
    exposure
    Capsaicin, dihydrocapsaicin, capsiate, eugenol, guaiacol, zingerone, vanillin, vanillylamine, vanillic acid, olvanil and curcumin, against procaine
    limitations
    An isolated nerve preparation with a clean negative control for the receptor: capsazepine did not block the effect and resiniferatoxin, a more powerful TRPV1 agonist, had none. That makes this a non-TRPV1 action of both compounds.
    nutrient_topic
    Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. · Dihydrocapsaicin
    organism
    Frog
    plain_language
    This block is not the famous receptor at work: blocking the receptor does not stop it, and a stronger agonist does not cause it.
    primary_references
    [dhc-p23352977] Inhibition by capsaicin and its related vanilloids of compound action potentials in frog sciatic nerves. (2013). https://pubmed.ncbi.nlm.nih.gov/23352977/ DOI: 10.1016/j.lfs.2013.01.011
    tissue_or_cell_type
    Sciatic nerve

    Dihydrocapsaicin: the second capsaicinoid, the hypothermia it is used to induce, what the gut and liver do to it, and what it does without TRPV1 (2026-09-21) · lines 127–138

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Compound action potentials recorded from frog sciatic nerve fibres by the air-gap method · source_derived_draft · unverified_draft

    ### dhc-conduction-block-not-trpv1 Capsaicin reversibly and concentration-dependently reduced the peak amplitude of the compound action potential, the TRPV1 antagonist capsazepine did not affect this activity, and the powerful TRPV1 agonist resiniferatoxin had no effect on compound action potentials, indicating no involvement of TRPV1 channels; capsaicin analogs and other vanilloids inhibited them in the same concentration-dependent way. Condition category: normal nutrient_topic: Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. plain_language: This block is not the famous receptor at work: blocking the receptor does not stop it, and a stronger agonist does not cause it. organism: Frog tissue_or_cell_type: Sciatic nerve experimental_model: Compound action potentials recorded from frog sciatic nerve fibres by the air-gap method limitations: An isolated nerve preparation with a clean negative control for the receptor: capsazepine did not block the effect and resiniferatoxin, a more powerful TRPV1 agonist, had none. That makes this a non-TRPV1 action of both compounds. exposure: Capsaicin, dihydrocapsaicin, capsiate, eugenol, guaiacol, zingerone, vanillin, vanillylamine, vanillic acid, olvanil and curcumin, against procaine evidence_span: {"source_cache": "artifacts/dihydrocapsaicin-research/23352977.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8a2b1f1a1bde0cfc3d08340f1951d88fb3711df6a40634a8c4c7bac63f8384bb", "start_char": 0, "end_char": 1707, "text_sha256": "8a2b1f1a1bde0cfc3d08340f1951d88fb3711df6a40634a8c4c7bac63f8384bb"} [dhc-p23352977] Inhibition by capsaicin and its related vanilloids of compound action potentials in frog sciatic nerves. (2013). https://pubmed.ncbi.nlm.nih.gov/23352977/ DOI: 10.1016/j.lfs.2013.01.011
    Complete structured claim and evidence

In the sources

Preserved passages that mention this component, quoted exactly. Open one to read it in context.

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