更新于：2024-11-01

TRPV1 x calcium channel x Sodium channels

更新于：2024-11-01

基本信息

关联

项与 TRPV1 x calcium channel x Sodium channels 相关的药物

iQ-008

靶点

Sodium channels x TRPV1 x calcium channel

作用机制

钠通道阻滞剂 [+2]

在研机构

iQure Pharma Inc.初创企业

原研机构

iQure Pharma Inc.初创企业

在研适应症

神经痛

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 TRPV1 x calcium channel x Sodium channels 相关的临床结果

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100 项与 TRPV1 x calcium channel x Sodium channels 相关的转化医学

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0 项与 TRPV1 x calcium channel x Sodium channels 相关的专利（医药）

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项与 TRPV1 x calcium channel x Sodium channels 相关的文献（医药）

2021-03-29·Pain Physician3区 · 医学

Receptor and Molecular Targets for the Development of Novel Opioid and Non-Opioid Analgesic Therapies

3区 · 医学

Review

作者: Urman, Richard D ; Chen, Rosalyn ; Coppes, O J Michael

BACKGROUND: Although conventional pain relief therapeutics have centered around μ-opioid agonists, these drugs are limited by adverse side effects, including respiratory depression and addiction potential. The ongoing opioid epidemic has galvanized research into novel analgesic therapies with more favorable profiles. New pharmacologic agents have been developed to target neuronal pathways involved in pain sensation. Certain receptors have been recognized to mediate nociceptive transmission, central sensitization, and the development of chronic pain states. OBJECTIVES: We conducted a literature review to identify potential targets for novel analgesic therapies. STUDY DESIGN: This study is a narrative review of potential analgesic targets. We characterize their antinociceptive mechanisms of action and evaluate their therapeutic potential. METHODS: A systemized search of available literature on novel analgesics was performed. A search was performed through the PubMed database to identify articles with key words of “novel analgesics,” “novel non-opioid analgesics,” “novel pain targets,” and “non-opioid analgesics.” Potential drug classes were identified and researched through corresponding keywords, with an emphasis on publications from 2018 to 2020. Older articles were included if frequently referenced by current literature. RESULTS: Potential novel analgesic targets include Nav1.7, Nav1.8, CaV2.2, and transient receptor potential vanilloid-1 (TRPV1) cation channel receptors in the peripheral nervous system. Other approaches disrupt the synthesis of pronociceptive signaling molecules such as nitric oxide, prostaglandin E2, and interleukin-6 (IL-6). Within central pain pathways, modification of -opioid, -opioid, N-methyl-D-aspartate, and cannabinoid receptors have been investigated in chronic pain and hyperalgesia models. Recent advances in molecular technology have also presented opportunities to modify protein expression or the cellular genome altogether. LIMITATIONS: Several analgesic targets have only demonstrated efficacy in preclinical trials. There are limited data evaluating the long-term safety profiles of therapies further on in development. CONCLUSIONS: We provide an overview of potential analgesic therapies in various stages of development, which may become clinically relevant in the near future. Some drugs such as TRPV1 agonists, anti-IL-6, and anti-nerve growth factor antibodies have demonstrated analgesic effect in specific clinical pain states. KEY WORDS: Nav1.7, Cav2.2, TRPV1, mPGES-1, IL-6, FAAH, NGF, gene therapy

2020-09-01·European Journal of Pharmacology3区 · 医学

Role of H2S in pain: Growing evidences of mystification

3区 · 医学

Review

作者: Guo, Jie ; Li, Gaofeng ; Yang, Le

There have been studies suggesting the pain attenuating as well as pain inducing actions of hydrogen sulfide (H₂S). Exogenous administrated H₂S may be antinociceptive or pronociceptive, while the endogenous H₂S is pronociceptive. Experimental studies have shown that pharmacological inhibitors of H₂S biosynthetic enzymes may attenuate nociceptive as well as neuropathic pain. It suggests that nerve injury or inflammatory agents may induce the expression of H₂S biosynthetic enzymes to increase the endogenous production of H₂S, which acts as a pain neurotransmitter to produce pain. The endogenous H₂S may act through different mechanisms including opening of T-type calcium channels, activation of voltage-gated sodium channels, suppression of potassium channels, activation of TRPA1, TRPV1 and TRPC6 channels, upregulation of spinal NMDA receptors and sensitization of purinergic receptors. Exogenous administration of H₂S/precursors/donors attenuates or facilitates pain. It may be hypothesized that local administration of H₂S may cause pain; while it's systemic administration may attenuate pain. The doses of H₂S may also influence the pain response and H₂S in low doses may contribute in reducing pain, while H₂S in high doses may contribute in relieving pain. Accordingly, enzymatic inhibitors of H₂S synthesis or systemic administration of slow H₂S releasing agents/low dose H₂S donors may be useful in attenuating nociceptive and neuropathic pain. The present review describes the dual role of H₂S in pain attenuation and pain induction along with possible mechanisms.

2014-10-01·Scandinavian Journal of Pain

Exonic mutations in SCN9A (Na_V1.7) are found in a minority of patients with erythromelalgia

Article

作者: Schmelz, Martin ; Whiteley, Jessica ; Helås, Tormod ; Quiding, Hans ; Centerholt, Carina ; Zhang, Zhiping ; Kvernebo, Mari Skylstad ; Lunden, Lars Kristian ; Juréus, Anna ; Kleggetveit, Inge-Petter ; Carr, Thomas Hedley ; Ørstavik, Kristin ; Jørum, Ellen ; Segerdahl, Märta ; Salter, Hugh

AbstractBackground and aim“Gain-of-function” mutations in voltage-gated sodium channel NaV1.7 have been linked to erythromelalgia (EM), characterized by painful hot and red hands and feet. We investigated the proportion of patients with EM that carry a mutation in NaV1.7 or in other pain-related genes and studied possible clinical differences.MethodsIn this study, 48 patients with EM were screened for mutations in a total of 29 candidate genes, including all sodium channel subunits, transient receptor potential channels (TRPA1, TRPV1, TRPM8), neurotrophic factors (NGF, NGFR, BDNF, GDNF, NTRK1 and WNK1) and other known pain-related genes (CACNG2, KCNS1, COMT, P2RX3, TAC1, TACR1), using a combination of next generation sequencing and classical Sanger sequencing.ResultsIn 7/48 patients protein-modifying mutations of NaV1.7 (P187L, I228M, I848T (n = 4) and N1245S) were identified. Patients with the I848T mutation could be identified clinically based on early onset and severity of the disease. In contrast, there were no clinical characteristics that differentiated the other patients with NaV1.7 mutation from those patients without. We also found more than twenty rare protein-modifying genetic variants in the genes coding for sodium channels (NaV1.8, NaV1.9, NaV1.6, NaV1.5, NaV2.1, SCN1B, SCN3B), transient receptor potential channel (TRPA1, TRPV1), and other pain-related targets (WNK1 and NGFR).ConclusionWe conclude that functionally characterized mutations of NaV1.7 (I848T) are present only in a minority of patient with EM. Albeit the majority of patients (27/48) carried rare protein-modifying mutations the vast majority of those will most probably not be causally linked to their disease.ImplicationsThe key question remaining to be solved is the possible role of rare variants of NaV1.8, NaV1.9, or beta-subunits in provoking chronic pain conditions or even EM.