{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:37:46Z","timestamp":1791221866461,"version":"4.1.0"},"reference-count":55,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T00:00:00Z","timestamp":1772841600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Jagiellonian University Collegium Medicum","award":["N42\/DBS\/000241"],"award-info":[{"award-number":["N42\/DBS\/000241"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MPs"],"abstract":"<jats:p>The present study was to evaluate the analgesic activity of two newly synthesized 1H-pyrrolo[3,4-c]pyridine-1,3(2H)-dione derivatives, designated DSZ-13 and DSZ-19. To achieve the desired result, the in vitro XTT cell proliferation assay, serotonin 5-HT1A receptor affinity and COX-1 and COX-2 enzyme inhibition potential of the compounds were conducted by real-time qPCR. Non-compartmental analysis was used to estimate the pharmacokinetic parameters of the compounds in serum and brain tissue. The analgesic activity was evaluated using various in vivo pain models, encompassing acute pain (hot plate test), tonic pain (formalin test), neurogenic pain (capsaicin test), carrageenan-induced acute inflammation, and neuropathic pain models. Both compounds showed moderate affinity for serotonin 5-HT1A receptors, a lack of cytotoxic activity, desirable pharmacokinetic parameters and slightly reduced mRNA expression for COX-1 and COX-2. Only the DSZ-19 revealed central\/supraspinal analgesic activity and did not affect movement. Both compounds attenuated tonic and neurogenic pain, in the formalin and capsaicin tests, respectively. In addition, the involvement of the 5-HT1A receptors in the formalin test was confirmed. Both compounds also showed antiallodynic activity in the oxaliplatin- and streptozotocin-induced neuropathy models. Slightly weaker than indomethacin, DSZ-13 and DSZ-19 attenuated carrageenan-induced inflammation (edema) and hyperalgesia in rat models.<\/jats:p>","DOI":"10.3390\/mps9020041","type":"journal-article","created":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T11:06:52Z","timestamp":1773054412000},"page":"41","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Searching for Mechanisms of Analgesic Activity in the Group of 1H-Pyrrolo[3,4-c]pyridine-1,3(2H)-dione Derivatives\u2014In Vitro and In Vivo Studies"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6377-5749","authenticated-orcid":false,"given":"Anna","family":"Dziubina","sequence":"first","affiliation":[{"name":"Department of Pharmacodynamics, Faculty of Pharmacy, Jagiellonian University Medical College, 9 Medyczna St., 30-688 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6543-4753","authenticated-orcid":false,"given":"Dominika","family":"Szkatu\u0142a","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, Wroclaw Medical University, 211 Borowska St., 50-556 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8619-5659","authenticated-orcid":false,"given":"Ma\u0142gorzata","family":"Szafarz","sequence":"additional","affiliation":[{"name":"Department of Pharmacokinetics and Physical Pharmacy, Faculty of Pharmacy, Jagiellonian University Medical College, 9 Medyczna St., 30-688 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5321-9266","authenticated-orcid":false,"given":"Agata","family":"Siwek","sequence":"additional","affiliation":[{"name":"Department of Pharmacobiology, Faculty of Pharmacy, Jagiellonian University Medical College, 9 Medyczna St., 30-688 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marek","family":"Kowalski","sequence":"additional","affiliation":[{"name":"Student Scientific Group of Pharmaceutical Chemistry, Department of Medicinal Chemistry, Wroclaw Medical University, 211 Borowska St., 50-556 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3501-8350","authenticated-orcid":false,"given":"Joanna","family":"Gdula-Argasi\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Pharmacobiology, Faculty of Pharmacy, Jagiellonian University Medical College, 9 Medyczna St., 30-688 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,7]]},"reference":[{"key":"ref_1","first-page":"133","article-title":"Synthesis and Properties of 2-(4-Substituted)Butyl Derivatives of Some 2,3-Dihydro-1,3-Dioxo-1 H-Pyrrolo[3,4-c]Pyridines","volume":"56","author":"Szkatula","year":"2001","journal-title":"Pharmazie"},{"key":"ref_2","first-page":"5013","article-title":"Synthesis and Biological Activity of Sulphadiazine Schiff\u2019s Bases of Isatin and Their N-Mannich Bases","volume":"19","author":"Singh","year":"2007","journal-title":"Asian J. 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