Aryl‐Urea Class and Related TRPV1 Antagonists

Gomtsyan, Arthur

doi:10.1002/9780470588284.ch11

Cited by 2 publications

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“…Considerable effort has been directed toward developing TRPV1 antagonists as novel antinociceptive agents. A number of antinociceptive small-molecule antagonists representing diverse chemotypes have been identified (Gomtsyan, 2010). Further characterization of several selective TRPV1 antagonists has defined a role for the channel in thermoregulation.…”

Section: Introductionmentioning

confidence: 99%

Pharmacology of Modality-Specific Transient Receptor Potential Vanilloid-1 Antagonists That Do Not Alter Body Temperature

Reilly

McDonald

Puttfarcken

et al. 2012

J Pharmacol Exp Ther

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The transient receptor potential vanilloid-1 (TRPV1) channel is involved in the development and maintenance of pain and participates in the regulation of temperature. The channel is activated by diverse agents, including capsaicin, noxious heat (Ն 43°C), acidic pH (Ͻ 6), and endogenous lipids including N-arachidonoyl dopamine (NADA). Antagonists that block all modes of TRPV1 activation elicit hyperthermia. To identify efficacious TRPV1 antagonists that do not affect temperature antagonists representing multiple TRPV1 pharmacophores were evaluated at recombinant rat and human TRPV1 channels with Ca 2ϩ flux assays, and two classes of antagonists were identified based on their differential ability to inhibit acid activation. Although both classes of antagonists completely blocked capsaicin-and NADA-induced activation of TRPV1, select compounds only partially inhibited activation of the channel by protons. Electrophysiology and calcitonin generelated peptide release studies confirmed the differential pharmacology of these antagonists at native TRPV1 channels in the rat. Comparison of the in vitro pharmacological properties of these TRPV1 antagonists with their in vivo effects on core body temperature confirms and expands earlier observations that acid-sparing TRPV1 antagonists do not significantly increase core body temperature. Although both classes of compounds elicit equivalent analgesia in a rat model of knee joint pain, the acid-sparing antagonist tested is not effective in a mouse model of bone cancer pain.

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Section: Introductionmentioning

confidence: 99%

Pharmacology of Modality-Specific Transient Receptor Potential Vanilloid-1 Antagonists That Do Not Alter Body Temperature

Reilly

McDonald

Puttfarcken

et al. 2012

J Pharmacol Exp Ther

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“…Канали TRP включають 6 підродин і 28 типів каналів, які відіграють важливу роль у сприйнятті тепла та кислого pH [28,29]. Вони в основному експресуються в нейронах, які посилають сенсорні сигнали вісцеральних органів, таких як простата, область навколо уретри, еякуляційні протоки, шкіра та м'язові структури сечостатевого тракту.При больових патологічних станах сечостатевих органів має місце збільшена експресія TRPV1 [30,31].…”

Section: ванілоїдні рецепториunclassified

Molecular Mechanisms of Nociception in Chronic Prostatitis

Gorpynchenko,

Nurimanov,

Nedogonova

2023

Clin. and prev. med.

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Introduction. The need to understand the pathophysiology of prostatitis is determined by its prevalence, usually chronic progressive course, significant impact on quality of life, fertility and sexuality. The modern arsenal of medicines allows us to achieve a clinically significant effect. Along with this, non-pharmacological methods are widely used to increase the effectiveness of treatment. However, despite significant successes in the treatment of prostatitis, the problems of insufficient efficiency remain unsolved by modern urology, and it is extremely difficult to help these patients. Understanding the pathophysiology of the disease has always been the key to successful diagnosis and treatment. That is why it is important to determine the mechanisms of development of painful manifestations of prostatitis. The aim. To describe the main molecular mechanisms of tissue damage reception, in particular of the prostate gland, which are perceived as pain sensations. Materials and methods. An evaluation of modern literature devoted to the mechanisms of creation of nerve impulses due to damage and inflammation of the prostate gland was carried out. The search was conducted in the MEDLINE and databases of the National Library of Ukraine named after V.I. Vernadsky. Results. The main molecular mechanisms of nociception in chronic prostatitis have been determined. A review of modern literature devoted to the study of pain mechanisms as a biologically significant signal of damage at the molecular level of reception is presented. Attention is focused on the features of nociception in prostatitis, its connection with the production of inflammatory mediators, possible mechanisms of hyperalgesia and allodynia. As a result of stress and tissue damage, the production and release of inflammatory mediators such as interleukins, interferon, prostaglandins, bradykinin, adenosine triphosphate, protons and nerve growth factor increase. These mediators activate pain receptors located on nerve endings and are ion channels of various types: transient receptor potential, acid, purinergic, and potassium ion leak channels. Conclusions. The presented literature data describe the mechanisms of nociception, hyperalgesia and allodynia in chronic prostatitis, the understanding of which can be the basis for the development of new methods of diagnosis and treatment.

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Aryl‐Urea Class and Related TRPV1 Antagonists

Cited by 2 publications

References 32 publications

Pharmacology of Modality-Specific Transient Receptor Potential Vanilloid-1 Antagonists That Do Not Alter Body Temperature

Pharmacology of Modality-Specific Transient Receptor Potential Vanilloid-1 Antagonists That Do Not Alter Body Temperature

Molecular Mechanisms of Nociception in Chronic Prostatitis

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