Научно-медицинский вестник Центрального ЧерноземьяНаучно-медицинский вестник Центрального Черноземья1990-472XФедеральное государственное бюджетное образовательное учреждение высшего образования "Воронежский государственный медицинский университет имени Н.Н. Бурденко" Министерства здравоохранения Российской Федерации1164410.18499/1990-472X-2026-27-2-4-10Analgesic activity and gastrotoxic effect of new alpha-cyanothioacetamide derivatives after chronic administration: an experimental comparative study in ratsivanovaelina03@mail.ruhelen_bibik@mail.ruvvbibik@gmail.comksg-group@mail.ruLugansk State Medical University named after St. Luke3006202627241005072026Copyright © 2026, Medical Scientific Bulletin of Central Chernozemye (Naučno-medicinskij vestnik Centralʹnogo Černozemʹâ)2026Objective. To evaluate the analgesic activity and gastotoxicity of four new alphacyanothioacetamide derivatives (AS-143, AS-144, f02-145, TD-0331) after chronic administration compared with reference NSAIDs (indomethacin, nimesulide, ibuprofen) and metamizole sodium. Materials and Methods. The study was performed on 90 outbred white male rats. Analgesic activity was assessed using the hot plate test (52 °C) by measuring the latency of the first behavioral reaction. Gastotoxicity was evaluated after 14-day administration by macroscopic examination of the gastric mucosa, ulceration index, and organometry. Results. All new compounds showed analgesic activity exceeding that of metamizole sodium. In animals receiving the alpha-cyanothioacetamide derivatives, no behavioral abnormalities or changes in appetite were observed. Macroscopic examination revealed no inflammation, edema, hyperemia, or erosive-ulcerative defects of the stomach; the ulceration index was zero, and organometric parameters did not differ from the intact control. In contrast, the indomethacin group demonstrated severe gastotoxicity: refusal of food, hypodynamia, 100% mortality on days 5–7, marked hyperemia, edema, multiple ulcers, and an increase in stomach size. Nimesulide and ibuprofen produced only isolated signs of toxicity (depressed activity, dull fur, hyperemia) with no fatalities. Conclusions. The new alpha-cyanothioacetamide derivatives, especially AS-144 and TD-0331, combine high analgesic potential with a favorable gastrointestinal safety profile, justifying further preclinical investigation.alpha-cyanothioacetamide derivatives, analgesic activity, hot plate test, gastotoxicityпроизводные альфа-цианотиоацетамида, анальгетическая активность, тест «горячая пластина», гастротоксичность