{"doi":"10.3897/pharmacia.70.e104828","title":"2ʹ,3,3,5ʹ-Tetramethyl-4ʹ-nitro-2ʹH-1,3ʹ-bipyrazole exerts antinociceptive effect using various nociception models","abstract":"<jats:p><jats:bold>Background</jats:bold>: 2ʹ,3,3,5ʹ-Tetramethyl-4ʹ-nitro-2ʹH-1,3ʹ-bipyrazole (TMNB) is a novel bipyrazole compound that exhibited antidiabetic and anti-inflammatory properties. However, its analgesic effect has not been investigated. This study aimed to assess the antinociceptive activity of TMNB using different nociception mouse models.</jats:p>\n          <jats:p><jats:bold>Methods</jats:bold>: TMNB doses (50, 100, 150, and 200 µg/kg) were assessed in mice using the acetic acid-induced writhing test, hot plate test, and formalin-induced paw licking assay. The effects were compared to those of mice treated with acetylsalicylic acid or morphine in the presence or absence of naloxone. Capsaicin- and glutamate-induced paw-licking tests were also used to evaluate the involvement of the vanilloid and glutamatergic systems, respectively.</jats:p>\n          <jats:p><jats:bold>Results</jats:bold>: TMNB produced significant dose-dependent inhibition of nociceptive behavior in the acetic acid-induced writhing test, showing 66% inhibition at a dose of 200 µg/kg. TMNB also caused a significant increase in the latency period in response to the hot plate test (68.2% at 200 µg/kg), and significantly inhibited both the neurogenic and inflammatory phases in the formalin-induced paw-licking test. Naloxone significantly reverses the effect of TMNB in both the hot plate test and formalin-induced paw-licking test. Moreover, TMNB significantly inhibited the neurogenic nociception induced by intraplantar injections of glutamate and capsaicin (53% and 77.1%, respectively at a dose of 200 µg/kg).</jats:p>\n          <jats:p><jats:bold>Conclusion</jats:bold>: TMNB possesses antinociceptive activity in mice that is mediated through both central and peripheral pathways.</jats:p>","journal":"Pharmacia","year":2023,"id":678846,"datarank":0.26876392038420827,"base_score":1.791759469228055,"endowment":1.791759469228055,"self_citation_contribution":0.26876392038420827,"citation_network_contribution":0.0,"self_endowment_contribution":0.26876392038420827,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1134236,"name":"Abdelrahim Alqudah","orcid":"0000-0003-3721-8225","position":1,"is_corresponding":false},{"id":1134235,"name":"Esam Qnais","orcid":"0000-0002-6203-4527","position":2,"is_corresponding":false},{"id":1134237,"name":"Mohammed Wedyan","orcid":"0000-0002-8693-5506","position":3,"is_corresponding":false},{"id":1773660,"name":"Kayed Abu-Safieh","orcid":"0000-0001-9810-1982","position":4,"is_corresponding":false},{"id":1134242,"name":"Omar Gammoh","orcid":"0000-0001-8801-2652","position":5,"is_corresponding":false},{"id":1134239,"name":"Yousra Bseiso","orcid":"0000-0002-4346-5049","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"2ʹ,3,3,5ʹ-Tetramethyl-4ʹ-nitro-2ʹH-1,3ʹ-bipyrazole exerts antinociceptive effect using various nociception models","abstract":"<jats:p><jats:bold>Background</jats:bold>: 2ʹ,3,3,5ʹ-Tetramethyl-4ʹ-nitro-2ʹH-1,3ʹ-bipyrazole (TMNB) is a novel bipyrazole compound that exhibited antidiabetic and anti-inflammatory properties. However, its analgesic effect has not been investigated. This study aimed to assess the antinociceptive activity of TMNB using different nociception mouse models.</jats:p>\n          <jats:p><jats:bold>Methods</jats:bold>: TMNB doses (50, 100, 150, and 200 µg/kg) were assessed in mice using the acetic acid-induced writhing test, hot plate test, and formalin-induced paw licking assay. The effects were compared to those of mice treated with acetylsalicylic acid or morphine in the presence or absence of naloxone. Capsaicin- and glutamate-induced paw-licking tests were also used to evaluate the involvement of the vanilloid and glutamatergic systems, respectively.</jats:p>\n          <jats:p><jats:bold>Results</jats:bold>: TMNB produced significant dose-dependent inhibition of nociceptive behavior in the acetic acid-induced writhing test, showing 66% inhibition at a dose of 200 µg/kg. TMNB also caused a significant increase in the latency period in response to the hot plate test (68.2% at 200 µg/kg), and significantly inhibited both the neurogenic and inflammatory phases in the formalin-induced paw-licking test. Naloxone significantly reverses the effect of TMNB in both the hot plate test and formalin-induced paw-licking test. Moreover, TMNB significantly inhibited the neurogenic nociception induced by intraplantar injections of glutamate and capsaicin (53% and 77.1%, respectively at a dose of 200 µg/kg).</jats:p>\n          <jats:p><jats:bold>Conclusion</jats:bold>: TMNB possesses antinociceptive activity in mice that is mediated through both central and peripheral pathways.</jats:p>","is_dataset_classified":null,"base_score":1.791759469228055,"endowment":1.791759469228055,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"21097893","pmcid":null,"openalex_id":"https://openalex.org/W4385197704","authors":[],"funders":[],"total_grants":0,"fwci":0.7045,"citation_percentile":0.6814181,"influential_citations":0,"citation_trend":[{"year":2024,"count":3},{"year":2025,"count":2}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://pharmacia.pensoft.net/article/104828/download/pdf/","host_type":"journal"},{"url":"https://pharmacia.pensoft.net/article/104828/download/pdf/","host_type":"publisher"},{"url":"https://pharmacia.pensoft.net/article/104828/download/xml/","host_type":"publisher"},{"url":"https://pharmacia.pensoft.net/article_preview.php?id=104828&skip_redirect=1","host_type":"publisher"},{"url":"https://doi.org/10.3897/pharmacia.70.e104828","host_type":"journal"},{"url":"https://zenodo.org/record/8185798","host_type":"repository"},{"url":"https://doaj.org/article/dc0cc99d855b462f8d6e218811444bd2","host_type":"repository"}],"fields_of_study":["Pain Mechanisms and Treatments","Pharmacological Effects of Natural Compounds","Bioactive Compounds and Antitumor Agents"],"mesh_terms":[],"keywords":["Licking","Nociception","Hot plate test","(+)-Naloxone","Capsaicin","Pharmacology","Chemistry","Morphine","Glutamate receptor","Analgesic","Anesthesia","Opioid","Medicine","Biochemistry","Receptor","2ʹ","3","5ʹ-Tetramethyl-4ʹ-nitro-2ʹH-1","3ʹ-bipyrazole","naloxone","vanilloid","glutamate"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-17T11:36:50.495504Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}