- |||||||||| azacitidine / Generic mfg.
Preclinical, Journal: Cooling-promoted myogenic differentiation of murine bone marrow mesenchymal stem cells through TRPM8 activation in (Pubmed Central) - Dec 17, 2023
We used 5-azacytidine as a myogenic differentiation inducer in murine bone marrow-derived MSCs...We observed that the TRPM8 antagonist counteracted the differentiation-promoting effect of the cooling. These results suggest that TRPM8 might modulate the multiple differentiation pathways of MSCs, and that cooling is an effective way of activating TRPM8, which regulates MSCs differentiation in
- |||||||||| NexoBrid (bromelain) / MediWound, Kaken Pharma, Teva
Journal: Bromelain regulates TRP channels to induce orofacial nociception relief in adult zebrafish. (Pubmed Central) - Dec 11, 2023
Moreover, capsaicin-induced desensitization effectively nullified the antinociceptive effect of bromelain. Collectively, these findings corroborate the therapeutic relevance of bromelain as a suppressor of orofacial nociception, which seems to be intricately connected to the modulation of TRP channels.
- |||||||||| YM-254890 / Astellas, Ventavis (iloprost) / Bayer, J&J, University of Copenhagen
Journal: Inhibition of TRPM8 function by the prostacyclin receptor requires coupling to Gq/11 proteins. (Pubmed Central) - Dec 4, 2023
Collectively, these findings corroborate the therapeutic relevance of bromelain as a suppressor of orofacial nociception, which seems to be intricately connected to the modulation of TRP channels. Our results demonstrate that an unusual signaling pathway of IP-R, namely the coupling to Gq/11 proteins, inhibits TRPM8, which may contribute to a better understanding of the role of TRPM8 and IP-R in the regulation of pain and inflammation.
- |||||||||| sirolimus / Generic mfg.
The immunosuppressant Rapamycin is an agonist of the cold-activated TRPM8 ion channel (WCC Halls A-C) - Nov 3, 2023 - Abstract #Neuroscience2023NEUROSCIENCE_8914;
Together, our results identify TRPM8 channels in sensory neurons as molecular targets of RAP, generalizing the agonist effect of macrolide immunosuppressants on this channel. These findings could help explain the anti-inflammatory effects of RAP after topical application to the skin and the eye surface.
- |||||||||| Journal: Melatonin promotes orofacial antinociception in adult zebrafish by modulating TRP channels. (Pubmed Central) - Jul 24, 2023
The molecular docking study indicated interaction between MT and the TRPV1, TRPA1 and TRPM8 channels and, in line with the in vivo results, there was greater affinity between MT and the TRPV1 channel. The results confirm the pharmacological relevance of melatonin as an inhibitor of orofacial nociception and this effect seems to be related to the modulation of TRP's channels.
- |||||||||| chloroquine phosphate / Generic mfg.
Preclinical, Journal: Topical borneol relieves nonhistaminergic pruritus via targeting TRPA1 and TRPM8 channels in peripheral nerve terminals of mice. (Pubmed Central) - Jun 30, 2023
Here, we showed that topical application of borneol on skin substantially suppressed pruritogen chloroquine- and compound 48/80-induced itching in mice...In contrast, the effect of borneol on compound 48/80-induced histaminergic itching occurs through TRPA1-and TRPM8-independent mechanisms. Our work demonstrates that borneol is an effective topical itch reliever, and TRPA1 inhibition and TRPM8 activation in peripheral nerve terminals account for its antipruritic effect.
- |||||||||| Lyfnua (gefapixant) / Merck (MSD)
Cough drugs and trials: truly novel medicines or is it all a placebo effect? (Coral 4+5) - Jun 17, 2023 - Abstract #ERS2023ERS_3024;
Other classes of drugs are emerging, including sodium channel blockers, NK1 antagonists, NMDA antagonists, TRPM8 agonists and opioid receptor agonists. This session will raise awareness of the above developments in this field.; Epidemiology; General respiratory patient care; Physiology
- |||||||||| ibuprofen / Generic mfg.
Preclinical, Journal: Neuronal loss of TRPM8 leads to obesity and glucose intolerance in male mice. (Pubmed Central) - May 8, 2023
This session will raise awareness of the above developments in this field.; Epidemiology; General respiratory patient care; Physiology Our data indicate that obesity in TRPM8-deficient mice is centrally mediated and likely originates from alterations in energy expenditure and/or thermal conductance, but does not depend on TRPM8 signaling in brown adipocytes or sensory neurons of the PVN.
- |||||||||| AX-8 / Axalbion
Randomized Proof-of-concept Study of AX-8, a TRPM8 Agonist, in Refractory or Unexplained Chronic Cough (Marriott Marquis Washington, Independence Ballroom Salons A-D (Level M4)) - Mar 25, 2023 - Abstract #ATS2023ATS_3860;
Subacute stimulation promotes brain plasticity further improving swallow function in older people with OD. This data suggests TRPM8 agonism shows potential for control of RCC/UCC as an alternative or adjunct to other therapies, especially in those patients complaining of cough driven by throat sensations.
- |||||||||| Review, Journal: Mutations of TRPM8 channels: Unraveling the molecular basis of activation by cold and ligands. (Pubmed Central) - Oct 6, 2022
Trying to make this review self-explicative and highly informative, important residues for TRPM8 function are summarized in a figure, and mutants, deletions and chimeras are compiled in a table, including also the observed effects by different methods of activation and the corresponding references. The information provided by this review may also help in the design of new ligands for TRPM8, an interesting biological target for therapeutic intervention.
- |||||||||| oxaliplatin / Generic mfg.
Journal: Establishment of the menthol test as a clinical evaluation method for oxaliplatin-induced neuropathy. (Pubmed Central) - Aug 13, 2022
Moreover, when the CDTs before and after administration were compared before grade exacerbation, there was a significant decrease in CDT after administration (P=0.04). By performing a menthol test in oxaliplatin-treated patients, it may be possible to objectively predict the exacerbation of peripheral neuropathy at an early stage.
- |||||||||| oxaliplatin / Generic mfg.
Preclinical, Journal: In vitro pain assay using human iPSC-derived sensory neurons and microelectrode array. (Pubmed Central) - Jun 30, 2022
The response to AITC increased in the presence of oxaliplatin in a concentration-dependent manner, suggesting that the increased cold sensitivity in humans can be reproduced in cultured hiPSC-derived sensory neurons. The in vitro MEA system using hiPSC-derived sensory neurons is an alternative method to animal experiments, and it is anticipated as a method for evaluating peripheral neuropathy and pain induced by compounds.
- |||||||||| AR-15512 / Aerie Pharma
Safety and Efficacy of a TRPM8 Agonist for the Treatment of Dry Eye Disease (WEWCC - Level 1, 144A) - Apr 26, 2022 - Abstract #ASCRSASOA2022ASCRS-ASOA_1234;
Conclusion AR-15512 is a TRPM8 agonist which represents a novel mechanism for treating subjects with DED. 0.003% AR-15512 has demonstrated early onset of action on signs and symptoms as well as continued symptom improvement over time.
- |||||||||| Journal: Transient Receptor Potential Melastatin 8, a sensor of cold temperatures mediates expression of cyclin-dependent kinase inhibitor, p21/Cip1, a regulator of epidermal cell proliferation. (Pubmed Central) - Mar 4, 2022
Unexpectedly, the TRPM8 blocker, used for the treatment of overactive bladder and bladder pain, N-(3-aminopropyl)-2-{[(3-methylphenyl) methyl] oxy}-N-(2-thienylmethyl) benzamide hydrochloride salt (AMTB) reduced DNA synthesis by upregulating p21/Cip1 expression. However, another TRPM8 blocker, N-(4-Tertiarybutylphenyl)-4-(3-chloropyridin- 2-yl) tetrahydropyrazine-1 (2H)-carbox-amide (BCTC), stimulated DNA synthesis by downregulating p21/Cip1 expression, indicating that it may pose a risk of carcinogenesis associated with dysregulated cell cycles when used to treat overactive bladder and bladder pain.
- |||||||||| Preclinical, Journal: Combination of TRP channel dietary agonists induces energy expending and glucose utilizing phenotype in HFD-fed mice. (Pubmed Central) - Feb 19, 2022
However, another TRPM8 blocker, N-(4-Tertiarybutylphenyl)-4-(3-chloropyridin- 2-yl) tetrahydropyrazine-1 (2H)-carbox-amide (BCTC), stimulated DNA synthesis by downregulating p21/Cip1 expression, indicating that it may pose a risk of carcinogenesis associated with dysregulated cell cycles when used to treat overactive bladder and bladder pain. The present work provides evidence that the new approach based on combination of sub-effective doses of TRP channel agonists (TRI-AGONIST) can be employed to develop concept-based functional food for therapeutic and preventive strategies against HFD-associated pathological complications.
- |||||||||| nitroprusside / Generic mfg.
Journal: The cold receptor TRPM8 activation leads to attenuation of endothelium-dependent cerebral vascular functions during head cooling. (Pubmed Central) - Dec 21, 2021
During the 3-h hypothermia period, responses of pial arterioles to endothelium-dependent dilators bradykinin and glutamate were reduced, whereas the responses to hypercapnia and an endothelium-independent dilator sodium nitroprusside (SNP) remained intact...AMTB counteracted the impairment of endothelium-dependent vasodilation caused by hypothermia or icilin. Overall, mild hypothermia produced by head cooling leads to acute reversible reduction of selected endothelium-dependent cerebral vasodilator functions via TRPM8 activation, whereas cerebral arteriolar smooth muscle functions are largely preserved.
- |||||||||| Tectin (tetrodotoxin) / WEX Pharma
Journal: Activation of TRPM8 channel inhibits contraction of the isolated human ureter. (Pubmed Central) - Nov 29, 2021
The TRPM8 channel expressed on sensory nerve terminals of the human ureter is involved in the inhibitory sensory neurotransmission and modulate ureter contraction via the CGRP-adenylyl cyclase-protein kinase A pathway. TRPM8 may be involved in stone-induced changes in ureter contraction or pain.
- |||||||||| tolimidone (MLR-1023) / Melior, Bukwang Pharma, Adhera Therap
Preclinical, Journal: MLR-1023 Treatment in Mice and Humans Induces a Thermogenic Program, and Menthol Potentiates the Effect. (Pubmed Central) - Nov 29, 2021
P2a
The TRPM8 agonist, menthol, potentiated the effect of MLR-1023 on the upregulation of genes for energy expenditure and insulin sensitivity in human adipocytes, and reduced fasting blood glucose in mice. The amplification of the thermogenic program by MLR-1023 and menthol in the absence of adrenergic activation will likely be well-tolerated, and bears investigation in a clinical trial.
- |||||||||| benzylpenicillin / Generic mfg.
Journal: Suppressive Effects of Transient Receptor Potential Melastatin 8 Agonist on Epileptiform Discharges and Epileptic Seizures. (Pubmed Central) - Oct 22, 2021
A previous report revealed the suppressive effects of transient receptor potential melastatin 8 (TRPM8) activation on penicillin G-induced epileptiform discharges (EDs)...In addition, TRPM8KO mice had a shorter firing latency of EDs, and EDs and epileptic seizures were deteriorated by the epilepsy inducer compared with those in WT mice, with the EDs being more easily propagated to the contralateral side. These findings suggest that TRPM8 activation in epileptic regions has anti-epileptic effects.
- |||||||||| Journal: Novel Putative Positive Modulators of α4β2 nAChRs Potentiate Nicotine Reward-Related Behavior. (Pubmed Central) - Sep 19, 2021
Using calcium flux assays, we determined that these ligands act as positive modulators (PMs) on α4β2 nAChRs. Due to α4β2 nAChRs' important role in nicotine dependence, as well as various neurological disorders including Parkinson's disease, the identification of these ligands as α4β2 nAChR PMs is an important finding, and they may serve as novel molecular tools for future nAChR-related investigations.
- |||||||||| docetaxel / Generic mfg.
Journal: Tune the channel: TRPM8 targeting in prostate cancer. (Pubmed Central) - Sep 14, 2021
As well, TRPM8 activation enhances the efficacy of docetaxel or enzalutamide in eradicating hormone naïve metastatic PCa cells. Overall, our findings provide a solid rationale for pursuing the pre-clinical and clinical study of TRPM8 as a valuable target for future approaches of precise oncology in PCa.
- |||||||||| Preclinical, Journal: Naked mole-rats lack cold sensitivity before and after nerve injury. (Pubmed Central) - Jul 29, 2021
We found increased TRPA1 messenger RNA, but decreased TRPM8 punctae in naked mole-rats when compared with mice. Our findings likely reflect species differences due to evolutionary environmental responses that are not easily explained by differences in receptor expression between the species.
- |||||||||| Journal: Diminished cold avoidance behaviours after chronic cold exposure - potential involvement of TRPM8. (Pubmed Central) - Jul 29, 2021
Primary sensory neuron soma are located in dorsal root ganglia (DRGs), and western blotting showed diminished TRPM8 levels in DRGs of Cold group mice, as compared to the Thermoneutral group. We conclude that acclimation to chronic cold altered thermosensory behaviours, so that mice appeared less cold sensitive, and potentially, TRPM8 is involved.
- |||||||||| Journal: Agonists of orally expressed TRP channels stimulate salivary secretion and modify the salivary proteome. (Pubmed Central) - Jul 3, 2021
In the case of nonivamide, these changes were attributed to functional shifts in the WMS secreted, primarily the over representation of salivary and non-salivary cystatins which was confirmed by immunoassay. This study provides new evidence of the impact of TRP channel agonists on the salivary proteome and the stimulation of salivary secretion by a TRPM8 channel agonist, which suggests that TRP channel agonists are potential candidates for developing treatments for sufferers of xerostomia.
- |||||||||| Journal: Improving brain power by applying a cool TRPM8 receptor agonist to the eyelid margin. (Pubmed Central) - May 15, 2021
The wipe solution contains a TRPM8 agonist called cryosim-3 (1-diisopropylphosphorylnonane) at 1-3 mg/mL in water and designed for delivery to the eyelid margin. Other sensory systems negatively affected by heat, such as the surfaces of the nasal cavity, can also be treated with the TRPM8 agonist as an adjunct to relieve discomfort from the heat.
- |||||||||| Journal: Calcium cytotoxicity sensitizes prostate cancer cells to standard-of-care treatments for locally advanced tumors. (Pubmed Central) - Apr 10, 2021
Here, we demonstrate that selective agonists of Transient Receptor Potential cation channel subfamily M member 8 (TRPM8), a cation channel characteristic of the prostate epithelium frequently overexpressed in advanced stage III/IV prostate cancers (PCa), sensitize therapy refractory models of PCa to radio, chemo or hormonal treatment. Overall, our study demonstrates that pharmacological-induced Ca cytotoxicity is an actionable strategy to sensitize cancer cells to standard therapies.
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