The TRPM8 inhibitor referred to as compound 5: molecular mechanisms & dependencies

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.

Human evidence only

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

The TRPM8 inhibitor compound 5 at 20 mg/kg subcutaneously augmented the drop in core temperature during cold exposure at 8 degrees, and when combined with dihydrocapsaicin at 1.25 to 2.5 mg/kg the drop in core temperature was amplified and prolonged, so that activating warm receptors and simultaneously inhibiting cold receptors potentiated the effect.
The TRPM8 inhibitor referred to as compound 5 → Hypothermia induced by a drug rather than by physical cooling source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dihydrocapsaicin-research/24595220.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f8844f6469d0412a4fabe00ebd706924083ebc2759c847bff9da104ae4404a87", "start_char": 0, "end_char": 1882, "text_sha256": "f8844f6469d0412a4fabe00ebd706924083ebc2759c847bff9da104ae4404a87"}
experimental_model
Controlled prospective study in conscious unrestrained young and aged male mice with implanted thermocouples and wireless transponders
exposure
Dihydrocapsaicin 2 to 4 mg/kg subcutaneously, alone and combined with the TRPM8 inhibitor compound 5 at 20 to 30 mg/kg
limitations
Includes aged animals, which most of this collection does not. Its finding that the effect does not desensitise is the direct opposite of the 1982 rat result and the two are recorded as conflicting.
nutrient_topic
Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. · Dihydrocapsaicin
organism
Mouse
plain_language
Blocking the cold sensor at the same time makes the cooling go deeper and last longer.
primary_references
[dhc-p24595220] Transient receptor potential melastatin 8 channel inhibition potentiates the hypothermic response to transient receptor potential vanilloid 1 activation in the conscious mouse. (2014). https://pubmed.ncbi.nlm.nih.gov/24595220/ DOI: 10.1097/ccm.0000000000000229
tissue_or_cell_type
Core temperature
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 283–294
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Controlled prospective study in conscious unrestrained young and aged male mice with implanted thermocouples and wireless transponders · source_derived_draft · unverified_draft
### dhc-trpm8-inhibition-potentiates The TRPM8 inhibitor compound 5 at 20 mg/kg subcutaneously augmented the drop in core temperature during cold exposure at 8 degrees, and when combined with dihydrocapsaicin at 1.25 to 2.5 mg/kg the drop in core temperature was amplified and prolonged, so that activating warm receptors and simultaneously inhibiting cold receptors potentiated the effect. 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: Blocking the cold sensor at the same time makes the cooling go deeper and last longer. organism: Mouse tissue_or_cell_type: Core temperature experimental_model: Controlled prospective study in conscious unrestrained young and aged male mice with implanted thermocouples and wireless transponders limitations: Includes aged animals, which most of this collection does not. Its finding that the effect does not desensitise is the direct opposite of the 1982 rat result and the two are recorded as conflicting. exposure: Dihydrocapsaicin 2 to 4 mg/kg subcutaneously, alone and combined with the TRPM8 inhibitor compound 5 at 20 to 30 mg/kg evidence_span: {"source_cache": "artifacts/dihydrocapsaicin-research/24595220.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f8844f6469d0412a4fabe00ebd706924083ebc2759c847bff9da104ae4404a87", "start_char": 0, "end_char": 1882, "text_sha256": "f8844f6469d0412a4fabe00ebd706924083ebc2759c847bff9da104ae4404a87"} [dhc-p24595220] Transient receptor potential melastatin 8 channel inhibition potentiates the hypothermic response to transient receptor potential vanilloid 1 activation in the conscious mouse. (2014). https://pubmed.ncbi.nlm.nih.gov/24595220/ DOI: 10.1097/ccm.0000000000000229
Complete structured claim and evidence

Where it participates (unsigned role)

TRPM8 ablation had no effect on total electromyographic muscle activity, on tachycardia, or on the drop in core temperature during cold exposure, with vehicle, compound 5 and TRPM8 knockout values closely similar across all three measures.
Experimental TRPM8 knockout mouse genotype → The cold-defence response that opposes induced cooling source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/dihydrocapsaicin-research/24005250.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e9d99ac4cc7a031474975ac4d7f3bcff0df922dc01047fe94bd51817ef5b3fea", "start_char": 0, "end_char": 1963, "text_sha256": "e9d99ac4cc7a031474975ac4d7f3bcff0df922dc01047fe94bd51817ef5b3fea"}
experimental_model
Conscious mice exposed to 10 degree cooling with implanted electromyography electrodes, electrocardiography and abdominal temperature transmitters
exposure
TRPV1 agonist dihydrocapsaicin or TRPM8 inhibitor compound 5, with TRPM8 knockout mice as a control
limitations
This is the record that explains why the drug is clinically interesting rather than merely cooling: it removes the defence that makes physical cooling intolerable in a conscious patient.
nutrient_topic
Dihydrocapsaicin research collection; topical membership is not evidence of a direct clinical effect, and dihydrocapsaicin is recorded separately from capsaicin. · Dihydrocapsaicin
organism
Mouse
plain_language
Deleting the cold receptor changed nothing about the body’s answer to cold.
primary_references
[dhc-p24005250] Shivering and tachycardic responses to external cooling in mice are substantially suppressed by TRPV1 activation but not by TRPM8 inhibition. (2013). https://pubmed.ncbi.nlm.nih.gov/24005250/ DOI: 10.1152/ajpregu.00296.2013
tissue_or_cell_type
Back muscle, heart and core
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 257–268
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Conscious mice exposed to 10 degree cooling with implanted electromyography electrodes, electrocardiography and abdominal temperature transmitters · source_derived_draft · unverified_draft
### dhc-trpm8-ablation-does-nothing TRPM8 ablation had no effect on total electromyographic muscle activity, on tachycardia, or on the drop in core temperature during cold exposure, with vehicle, compound 5 and TRPM8 knockout values closely similar across all three measures. 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: Deleting the cold receptor changed nothing about the body’s answer to cold. organism: Mouse tissue_or_cell_type: Back muscle, heart and core experimental_model: Conscious mice exposed to 10 degree cooling with implanted electromyography electrodes, electrocardiography and abdominal temperature transmitters limitations: This is the record that explains why the drug is clinically interesting rather than merely cooling: it removes the defence that makes physical cooling intolerable in a conscious patient. exposure: TRPV1 agonist dihydrocapsaicin or TRPM8 inhibitor compound 5, with TRPM8 knockout mice as a control evidence_span: {"source_cache": "artifacts/dihydrocapsaicin-research/24005250.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e9d99ac4cc7a031474975ac4d7f3bcff0df922dc01047fe94bd51817ef5b3fea", "start_char": 0, "end_char": 1963, "text_sha256": "e9d99ac4cc7a031474975ac4d7f3bcff0df922dc01047fe94bd51817ef5b3fea"} [dhc-p24005250] Shivering and tachycardic responses to external cooling in mice are substantially suppressed by TRPV1 activation but not by TRPM8 inhibition. (2013). https://pubmed.ncbi.nlm.nih.gov/24005250/ DOI: 10.1152/ajpregu.00296.2013
Complete structured claim and evidence

The events it takes part in

A mechanism often involves more than two components. These are the full events, with every participant and its role.

Situations it appears in

Low-supply and faulty-machinery situations recorded in the chapters where this component plays a part.

In the sources

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

Open hypotheses

Proposed ideas that involve this component. They are labeled as hypotheses and do not change any recorded statement.

This is a research prototype built from draft material. It is not medical advice, and its statements still await verification against the original studies.

The TRPM8 inhibitor referred to as compound 5