Repeated Administration of Vanilloid Receptor TRPV1 Antagonists Attenuates Hyperthermia Elicited by TRPV1 Blockade

Gavva, Narender R.; Bannon, Anthony W.; Hovland, David N.; Lehto, Sonya G.; Klionsky, Lana; Surapaneni, Sekhar; Immke, David; Henley, Charles M.; Arik, Leyla; Bak, Annette; Davis, James; Ernst, Nadia; Hever, Gal; Kuang, Rongzhen; Shi, Licheng; Tamir, Rami; Wang, Jue; Wang, Weiya; Zajic, Gary; Zhu, Dawn; Norman, Mark H.; Louis, Jean‐Claude; Magal, Ella; Treanor, James

doi:10.1124/jpet.107.125674

Cited by 157 publications

(127 citation statements)

References 39 publications

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“…Several highly selective TRPV1 antagonists have advanced into clinical development for the treatment of pain. [30,31] One of these TRPV1 antagonists, SB-705498 has been recently trialed in the treatment of refractory CC [32]. …”

Section: Introductionmentioning

confidence: 99%

An update and systematic review on drug therapies for the treatment of refractory chronic cough

Ryan

Vertigan

Birring

2018

Expert Opinion on Pharmacotherapy

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Introduction: Chronic Cough (CC) is common and often associated with significant comorbidity and decreased quality of life. In up to 50% of cases, the cough is refractory despite extensive investigation and treatment trials. It is likely that the key abnormality in refractory CC is dysfunctional, hypersensitive sensory nerves, similar to conditions such as laryngeal hypersensitivity and neuropathic pain.Areas covered: The aim of this systematic review is to assess drug therapies for refractory CC. The authors review the current management of CC and provide discussion of the similarities between neuropathic pain and refractory CC. They review repurposed and new pharmacological treatments. Several meta-analyses were performed to compare the efficacy of treatments where possible.Expert opinion: Repurposed pain medications such as gabapentin and pregabalin reduce the frequency of cough and improve quality of life. Along with speech pathology, they are important and alternate treatments for refractory CC. However, more treatments are needed and the P2X3 ion channel receptor antagonists show the most promise. With a better understanding of neuronal activation and sensitisation and their signal processing in the brain, improved animal models of cough, and the use of validated cough measurement tools, more effective treatments will develop.

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Section: Introductionmentioning

confidence: 99%

An update and systematic review on drug therapies for the treatment of refractory chronic cough

Ryan

Vertigan

Birring

2018

Expert Opinion on Pharmacotherapy

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“…Similar to agonist-induced hypothermia that disappears after repeated administration, antagonist-induced hyperthermia also shows attenuation after repeated dosing [126]. It was suggested that the initial hyperthermia can be adequately managed by common antipyretic agents like acetaminophen.…”

Section: Hyperthermia Caused By Trpv1 Blockadementioning

confidence: 99%

TRPV1 Antagonists as Analgesic Agents

Trevisani

Gatti²

2013

TOPAINJ

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Abstract:The last decade (2001 -2010), declared as the Decade of Pain Control and Research by the United States Congress, brought significantly advances in our understanding of pain biology. Unfortunately, this has not translated into additional effective treatments of chronic pain conditions. Chronic pain is a debilitating and complex clinical state usually associated with diabetic neuropathy, postherpetic neuralgia, low back pathology, fibromyalgia, and neurological disorders. Standard pain drugs, even narcotic opioid analgesic agents, often provide unsatisfactory pain relief while causing important side-effect such as sedation, tolerance, dependence, respiratory depression and constipation. Furthermore, the effective management of chronic pain needs a multidisciplinary management approach and still represents one of the most urgent unmet medical need. Recently, preclinical research has uncovered new molecular mechanisms underlying the generation and transduction of pain, many of which represent new targets for innovative pharmacological interventions. This review focuses on Transient Receptor Potential (TRP) Vanilloid Type 1 (TRPV1) channel as a target for treating chronic pain. TRPV1 is a multifunctional ion channel involved in thermosensation (heat) and taste perception. Importantly, TRPV1 also functions as a molecular integrator for a broad variety of seemingly unrelated noxious stimuli. Indeed, TRPV1 is thought to be a major transducer of the thermal hyperalgesia that follows inflammation and/or tissue injury. Desensitization to topical TRPV1 agonists (e.g. capsaicin creams and patches) has been in clinical use for decades to treat chronic painful conditions like diabetic neuropathy. Most recently, a number of potent, small molecule TRPV1 antagonists have been advanced into clinical trials for pain relief. Perhaps not unexpectedly given the prominent role of TRPV1 in thermosensation, some of these antagonists showed worrisome adverse effects (hyperthermia and impaired noxious heat sensation) in humans, leading to their withdrawal from clinical trials. However, recent reports of TRPV1 antagonists that do not affect core body temperature in preclinical species suggest a potential opportunity to reduce at least this important side effect.

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“…17 TRPV1 is activated by numerous stimuli including heat (>42 C), vanilloids, lipids, and protons/cations. Several highly selective TRPV1 antagonists have advanced into clinical development for the treatment of pain including 11 AMG517, 18 12 SB-705498, 19 13 ABT-102, 20 and 14 MK-2295 21 (Fig. 5).…”

Section: Ion Channel Modulators For Pain Therapy In Clinical Developmentmentioning

confidence: 99%

Ion channel therapeutics for pain

Skerratt

West

2015

Channels

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Repeated Administration of Vanilloid Receptor TRPV1 Antagonists Attenuates Hyperthermia Elicited by TRPV1 Blockade

Cited by 157 publications

References 39 publications

An update and systematic review on drug therapies for the treatment of refractory chronic cough

An update and systematic review on drug therapies for the treatment of refractory chronic cough

TRPV1 Antagonists as Analgesic Agents

Ion channel therapeutics for pain

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