Study of Anti-inflammatory Activity of a New Non-opioid Analgesic on the Basis of a Selective Inhibitor of TRPA1 Ion Channels

Бесхмельницына, Е. А.; Pokrovsky, M. V.; Куликов, Александр Леонидович; Peresypkina, Anna A.; Varavin, Evgeniy I.

doi:10.2174/1871523018666190208123700

Cited by 3 publications

(2 citation statements)

References 25 publications

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“…The possibility of treatment of acute pain with TRPA 1 antagonists was shown in preclinical studies. In the study of Beskhmelnitsyna et al (2018;2019a;2019b), the compound ZC02-0012 showed analgesic activity superior to that of ketorolac according to hot plate and acetic acid-induced writhing tests, as well as anti-inflammatory activity, comparable to that of diclofenac sodium. Intraplantar injection of AR18 reduced mechanical hyperalgesia in wild-type mice and had no effect in mice with TRPA 1 genetic knockout (Petrus et al 2007).…”

Section: Trpa 1 Antagonistsmentioning

confidence: 97%

Transient receptor potential Ankyrin 1: structure, function and ligands

Pyatigorskaya¹,

Филиппова²,

Nikolenko³

et al. 2022

RRP

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Introduction: Transient receptor potential ankyrin 1 (TRPA1) is a protein expressed in many living organisms. During the study of TRPA1, its unique biological role as a universal and polymodal sensor of various altering agents was found. The aim of this study is to search and generalize information about structural features and molecular determinants, mechanisms of activation, action and modulation of TRPA1 as a universal pain and inflammation sensor, as well as the nature of activators and antagonists of this target and their therapeutic potential. Materials and methods: This article presents an overview of the results of scientific research of TRPA1, its modulators, as well as an overview of their pharmacological potential over the period from the discovery of these channels to the present, with an emphasis on the last decade. Results and discussion: The main collected data on expression, structural features and molecular determinants, mechanisms of activation and action of TRPA1 indicate its role as a universal and labile element of the primary response of the body to adverse exogenous and endogenous factors. Regardless of the nature of the stimulus, hyperstimulation of TRPA1 channels can lead to such phenomena as pain, inflammation, itching, edema and other manifestations of alteration, and therefore TRPA1 blockade can be used in the treatment of various diseases accompanied by these pathological conditions. Currently, TRPA1 antagonists are being actively searched for and studied, as evidenced by a high patent activity over the past 14 years; however, the molecular mechanisms of action and pharmacological properties of TRPA1 blockers remain understudied. Conclusion: Acquire of new information about TRPA1 will help in the development of its modulators, which can become promising analgesics, anti-inflammatory drugs, bronchodilators, and agents for the treatment of cardiovascular diseases of new generations.

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Section: Trpa 1 Antagonistsmentioning

confidence: 97%

Transient receptor potential Ankyrin 1: structure, function and ligands

Pyatigorskaya¹,

Филиппова²,

Nikolenko³

et al. 2022

RRP

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“…Несмотря на стремительное развитие экспериментальной фармакологии [4,[25][26][27][28], совершенствование методов направленного синтеза, позволяющих создавать высокоселективные препараты, остаётсявысокоактуальнымпоискновыхсоединений. Потенциальными кандидатами с нейропротективными свойствами могут быть производные этилтиадиазола.…”

Section: Introductionunclassified

The Search for Neuroprotective Compounds Among New Ethylthiadiazole Derivatives

Cherevatenko

Antsiferov

Skachilova

et al. 2021

Farm. farmakol. (Pâtigorsk)

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The aim of the study is to search compounds with neuroprotective properties among new ethylthiadiazole derivatives in simulated traumatic brain injury.Materials and methods. The experiment was carried out on 78 white male rats 270±20 g line “Wistar” 5–6 months of age and 120 outbred sexually mature mice weighing 20±2 grams. The article describes the search for compounds with neuroprotective properties among new ethylthiadiazole derivatives under the codes LKHT 4–15, LKHT 10–18, LKHT 11–18, and LKHT 12–18 in experimental traumatic brain injury in rats. Acute toxicity of the compounds was studied. Pharmacological screening was performed using behavioral and neurological research methods. The McGraw stroke score scale modified by I.V. Gannushkina and the mNSS psychometric scale were used in the study. The open field and Rota-rod tests were used to assess the behavioral status of the animals.Results. The compound-LKHT 12–18 at a dose of 50 mg/kg was detected as a leader. In pharmacological correction of pathology, this compound had the lowest percentage of fatality among the studied compounds (8%), the severity of neurological deficit was significantly reduced, the lowest scores and a higher level of motor activity of the limbs were registered. The number of rearing in the group of animals receiving the compound LKHT 12–18 at the dose of 50 mg/kg increased by 1.5 times, statistically significant (p<0.05) in comparison with the control group. Based on the results of the “Rota-rod” test, the total time of holding animals on the rod for 3 attempts was statistically significantly different in the groups administered with LKHT 12–18 derivatives (1.5 times longer) at the dose of 50 mg/kg compared with the control (p<0.05).Conclusion. Based on the results obtained in this study, it is planned to study in more detail the compound LKHT 12–18 at the dose of 50 mg/kg.

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Diversity analysis of sea anemone peptide toxins in different tissues of Heteractis crispa based on transcriptomics

Guo,

Fu,

Yuan

et al. 2024

Sci Rep

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Peptide toxins found in sea anemones venom have diverse properties that make them important research subjects in the fields of pharmacology, neuroscience and biotechnology. This study used high-throughput sequencing technology to systematically analyze the venom components of the tentacles, column, and mesenterial filaments of sea anemone Heteractis crispa, revealing the diversity and complexity of sea anemone toxins in different tissues. A total of 1049 transcripts were identified and categorized into 60 families, of which 91.0% were proteins and 9.0% were peptides. Of those 1049 transcripts, 416, 291, and 307 putative proteins and peptide precursors were identified from tentacles, column, and mesenterial filaments respectively, while 428 were identified when the datasets were combined. Of these putative toxin sequences, 42 were detected in all three tissues, including 33 proteins and 9 peptides, with the majority of peptides being ShKT domain, β-defensin, and Kunitz-type. In addition, this study applied bioinformatics approaches to predict the family classification, 3D structures, and functional annotation of these representative peptides, as well as the evolutionary relationships between peptides, laying the foundation for the next step of peptide pharmacological activity research.

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Study of Anti-inflammatory Activity of a New Non-opioid Analgesic on the Basis of a Selective Inhibitor of TRPA1 Ion Channels

Cited by 3 publications

References 25 publications

Transient receptor potential Ankyrin 1: structure, function and ligands

Transient receptor potential Ankyrin 1: structure, function and ligands

The Search for Neuroprotective Compounds Among New Ethylthiadiazole Derivatives

Diversity analysis of sea anemone peptide toxins in different tissues of Heteractis crispa based on transcriptomics

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