Russian veterinary journal Russian veterinary journal Российский ветеринарный журнал 2500-4379 103992 10.32416/2500-4379-2025-3-21-32 СОВРЕМЕННЫЕ ФАРМАКО- И БИОПРЕПАРАТЫ MODERN PHARMACOLOGICAL DRUGS & BIOPREPARATIONS СОВРЕМЕННЫЕ ФАРМАКО- И БИОПРЕПАРАТЫ Pharmacotoxicological evaluation of a new original medicinal product for dogs Trazapentine® tablets (succinate trazodone + gabapentin) Фармакологическая характеристика и токсикологические параметры нового оригинального препарата для собак Тразапентин® таблетки (сукцинат тразодона + габапентин) Кузьминова Елена Васильевна Kuz'minova Elena Vasil'evna

доктор ветеринарных наук;

doctor of veterinary sciences;

 Белоглазов Денис Валерьевич Beloglazov Denis Valer'evich

кандидат биологических наук;

candidate of sciences in biology;

 Мукасеев Сергей Владимирович Mukaseev Sergey Vladimirovich

кандидат ветеринарных наук;

candidate of veterinary sciences;

 Пархоменко Сергей Александрович Parhomenko Sergey Aleksandrovich Зейналов Орхан Ахмедович Zeynalov Orhan Ahmedovich

кандидат биологических наук;

candidate of sciences in biology;

 Краснодарский научный центр по зоотехнии и ветеринарии Краснодар Россия Краснодарский научный центр по зоотехнии и ветеринарии Краснодар Russian Federation ООО «НПК «СКиФФ» Москва Россия LLC «NPC «SKiFF» Moscow Russian Federation ООО «АГ «Аспект» Москва Россия LLC AG Aspect Moscow Russian Federation ООО «НВП «Астрафарм» Москва Россия LLC «RDE «Astrapharm» Moscow Russian Federation ООО «НПК «СКиФФ» Москва Россия LLC «NPC «SKiFF» Moscow Russian Federation ООО «АГ «Аспект» Москва Россия LLC «AG «Aspect» Moscow Russian Federation ООО «НВП «Астрафарм» Москва Россия LLC «RDE «Astrapharm» Moscow Russian Federation ООО «БиоФерон» Москва Россия LLC «BioFeron» Moscow Russian Federation ООО «НВП «Астрафарм» Москва Россия LLC «RDE «Astrapharm» Moscow Russian Federation ООО «НПК «СКиФФ» Москва Россия LLC «NPC «SKiFF» Moscow Russian Federation ООО «НВП «Астрафарм» Москва Россия LLC «RDE «Astrapharm» Moscow Russian Federation ООО «БиоФерон» Москва Россия LLC «BioFeron» Moscow Russian Federation 22 09 2025 22 09 2025 2025 3 21 32 08 09 2025 https://logospress.editorum.ru/en/nauka/article/103992/view

В ходе исследования установлено, что абсолютная (LD100) и средняя (LD50) летальные дозы лекарственного препарата Тразапентин® таблетки для собак не определяются. По классификации ГОСТ 12.1.007-76 препарат отнесен к IV классу опасности ‒ вещества малоопасные. При изучении хронической токсичности не выявлено летальных исходов и негативного влияния на организм животных как в период введения препарата в течении 90 дней, так и после его отмены. Доказано отсутствие у препарата аллергизирующих и раздражающих свойств.

The study has established that the absolute (LD100) and median (LD50) lethal doses of the Trazapentin® tablets for dogs cannot be determined. According to the GOST 12.1.007-76 classification, the drug is classified as hazard class IV ‒ slightly hazardous substances. The study of chronic toxicity over a period of 90 days revealed no lethal outcomes or negative effects on the animals’ organisms, both during the administration period and after discontinuation of the Trazapentin®. The absence of allergenic and irritant properties of the drug has been proven.

 сукцинат тразодона габапентин Тразапентин® таблетки острая токсичность хроническая токсичность хроническая токсичность аллергизирующие свойства succinate trazodone gabapentin Trazapentin® tablets acute toxicity chronic toxicity allergenic properties

Белоглазов, Д.В. Оценка эффективности нового препарата Экспресс Успокоин® таблетки при ситуационной коррекции поведенческих проблем у кошек / Д.В. Белоглазов, С.В. Мукасеев, О.А. Зейналов // Российский ветеринарный журнал. – 2023. – № 2. – С. 14-22. – DOI 10.32416/2500-4379-2023-2-14-22. Beloglazov, D.V. Ocenka effektivnosti novogo preparata Ekspress Uspokoin® tabletki pri situacionnoy korrekcii povedencheskih problem u koshek / D.V. Beloglazov, S.V. Mukaseev, O.A. Zeynalov // Rossiyskiy veterinarnyy zhurnal. – 2023. – № 2. – S. 14-22. – DOI 10.32416/2500-4379-2023-2-14-22. Белоглазов, Д.В. Оценка эффективности нового препарата «Экспресс Успокоин® таблетки» при ситуационной коррекции поведенческих проблем у собак / Д.В. Белоглазов, С.В. Мукасеев, О.А. Зейналов // Современная ветеринарная медицина. – 2023. ‒ № 1. ‒ C. 18-22. Beloglazov, D.V. Ocenka effektivnosti novogo preparata «Ekspress Uspokoin® tabletki» pri situacionnoy korrekcii povedencheskih problem u sobak / D.V. Beloglazov, S.V. Mukaseev, O.A. Zeynalov // Sovremennaya veterinarnaya medicina. – 2023. ‒ № 1. ‒ C. 18-22. Елизарова, Е.А. Оценка эффективности нового лекарственного препарата Курс Успокоин таблетки для коррекции возрастных когнитивных нарушений у собак / Е.А. Елизарова, Д.В. Белоглазов, О.А Зейналов, С.В. Мукасеев // Российский ветеринарный журнал. ‒ 2024. ‒ № 3. ‒ С. 27-33. DOI 10.32416/2500-4379-2024-3-27-33. Elizarova, E.A. Ocenka effektivnosti novogo lekarstvennogo preparata Kurs Uspokoin tabletki dlya korrekcii vozrastnyh kognitivnyh narusheniy u sobak / E.A. Elizarova, D.V. Beloglazov, O.A Zeynalov, S.V. Mukaseev // Rossiyskiy veterinarnyy zhurnal. ‒ 2024. ‒ № 3. ‒ S. 27-33. DOI 10.32416/2500-4379-2024-3-27-33. Елизарова, Е.А. Оценка эффективности нового лекарственного препарата Курс Успокоин таблетки для коррекции возрастных когнитивных нарушений у кошек / Е.А. Елизарова, Д.В. Белоглазов, С.В. Мукасеев, О.А. Зейналов // Российский ветеринарный журнал. – 2024. – № 1. – С. 33-39. DOI 10.32416/2500-4379-2024-1-33-39. Elizarova, E.A. Ocenka effektivnosti novogo lekarstvennogo preparata Kurs Uspokoin tabletki dlya korrekcii vozrastnyh kognitivnyh narusheniy u koshek / E.A. Elizarova, D.V. Beloglazov, S.V. Mukaseev, O.A. Zeynalov // Rossiyskiy veterinarnyy zhurnal. – 2024. – № 1. – S. 33-39. DOI 10.32416/2500-4379-2024-1-33-39. Курс Успокоин таблетки. Инструкция по ветеринарному применению лекарственного препарата [Электронный ресурс]. https://galen.vetrf.ru/files/5c1ac33d-9461-4add-bd1c-e04b2d82f1fb (дата обращения 21.01.25). Kurs Uspokoin tabletki. Instrukciya po veterinarnomu primeneniyu lekarstvennogo preparata [Elektronnyy resurs]. https://galen.vetrf.ru/files/5c1ac33d-9461-4add-bd1c-e04b2d82f1fb (data obrascheniya 21.01.25). Приказ Министерства сельского хозяйства РФ №101 от 06.03.2018 г. «Об утверждении Правил проведения доклинического исследования лекарственного средства для ветеринарного применения, клинического исследования лекарственного препарата для ветеринарного применения, исследования биоэквивалентности лекарственного препарата для ветеринарного применения». Зарегистрирован в Минюсте России 05.06.2018 № 51296. Prikaz Ministerstva sel'skogo hozyaystva RF №101 ot 06.03.2018 g. «Ob utverzhdenii Pravil provedeniya doklinicheskogo issledovaniya lekarstvennogo sredstva dlya veterinarnogo primeneniya, klinicheskogo issledovaniya lekarstvennogo preparata dlya veterinarnogo primeneniya, issledovaniya bioekvivalentnosti lekarstvennogo preparata dlya veterinarnogo primeneniya». Zaregistrirovan v Minyuste Rossii 05.06.2018 № 51296. Руководство по проведению доклинических исследований лекарственных средств. Часть первая / А.Н. Миронов, Н.Д. Бунатян и др. – М.: Гриф и К, 2012. – 944 с. Rukovodstvo po provedeniyu doklinicheskih issledovaniy lekarstvennyh sredstv. Chast' pervaya / A.N. Mironov, N.D. Bunatyan i dr. – M.: Grif i K, 2012. – 944 s. Руководство по экспериментальному (доклиническому) изучению новых фармакологических веществ / Под ред. Р. У. Хабриева. – М.: Медицина, 2005. – 832 с. Rukovodstvo po eksperimental'nomu (doklinicheskomu) izucheniyu novyh farmakologicheskih veschestv / Pod red. R. U. Habrieva. – M.: Medicina, 2005. – 832 s. Смирнов, А.В. Янтарная кислота и ее применение в медицине. Часть I. Янтарная кислота: метаболит и регулятор метаболизма организма человека / А.В. Смирнов, О.Б. Нестерова, Р.В. Голубев // Нефрология. – 2014. – Т. 18. – № 2. – С. 33-41. Smirnov, A.V. Yantarnaya kislota i ee primenenie v medicine. Chast' I. Yantarnaya kislota: metabolit i regulyator metabolizma organizma cheloveka / A.V. Smirnov, O.B. Nesterova, R.V. Golubev // Nefrologiya. – 2014. – T. 18. – № 2. – S. 33-41. Экспресс Успокоин® таблетки. Инструкция по ветеринарному применению лекарственного препарата [Электронный ресурс]. https://galen.vetrf.ru/files/41fc97ef-69b3-4502-bded-57bb87220cd6 (дата обращения 21.01.25). Ekspress Uspokoin® tabletki. Instrukciya po veterinarnomu primeneniyu lekarstvennogo preparata [Elektronnyy resurs]. https://galen.vetrf.ru/files/41fc97ef-69b3-4502-bded-57bb87220cd6 (data obrascheniya 21.01.25). Belshaw, Z. Assessment of quality of life and chronic pain in dogs / Z. Belshaw, J. Yeates // Vet J. ‒ 2018. ‒ No. 239. ‒ pp. 59-64. doi:10.1016/j.tvjl.2018.07.010. Belshaw, Z. Assessment of quality of life and chronic pain in dogs / Z. Belshaw, J. Yeates // Vet J. ‒ 2018. ‒ No. 239. ‒ pp. 59-64. doi:10.1016/j.tvjl.2018.07.010. Belinskaia, D.A. Psychotropic Drugs for the Management of Chronic Pain and Itch. / D.A. Belinskaia, M.A. Belinskaia, O.I. Barygin, N.P. Vanchakova, N.N. Shestakova // Pharmaceuticals (Basel). ‒ 2019. ‒ No. 12(2). ‒ pp. 99. doi:10.3390/ph12020099. Belinskaia, D.A. Psychotropic Drugs for the Management of Chronic Pain and Itch. / D.A. Belinskaia, M.A. Belinskaia, O.I. Barygin, N.P. Vanchakova, N.N. Shestakova // Pharmaceuticals (Basel). ‒ 2019. ‒ No. 12(2). ‒ pp. 99. doi:10.3390/ph12020099. Boyle, Y. The effect of a combination of gabapentin and donepezil in an experimental pain model in healthy volunteers: Results of a randomized controlled trial / Y. Boyle, D. Fernando, H. Kurz, S.R. Miller, M. Zucchetto, J. Storey // Pain. ‒ 2014. ‒ No. 155(12). ‒ pp. 2510-2516. doi: 10.1016/j.pain.2014.09.003. Boyle, Y. The effect of a combination of gabapentin and donepezil in an experimental pain model in healthy volunteers: Results of a randomized controlled trial / Y. Boyle, D. Fernando, H. Kurz, S.R. Miller, M. Zucchetto, J. Storey // Pain. ‒ 2014. ‒ No. 155(12). ‒ pp. 2510-2516. doi: 10.1016/j.pain.2014.09.003. Cashmore, R.G. Clinical diagnosis and treatment of suspected neuropathic pain in three dogs / R.G. Cashmore, T.R. Harcourt-Brown, P.M. Freeman, N.D. Jeffery, N. Granger // Aust Vet J. ‒ 2009. ‒ No. 87(1). ‒ pp. 45-50. doi:10.1111/j.1751-0813.2008.00379.x. Cashmore, R.G. Clinical diagnosis and treatment of suspected neuropathic pain in three dogs / R.G. Cashmore, T.R. Harcourt-Brown, P.M. Freeman, N.D. Jeffery, N. Granger // Aust Vet J. ‒ 2009. ‒ No. 87(1). ‒ pp. 45-50. doi:10.1111/j.1751-0813.2008.00379.x. Chea, B. Trazodone: a review of its pharmacological properties and its off-label use in dogs and cats / B. Chea, M. Giorgi // Am J Anim Vet Sci. ‒ 2017. ‒ No. 12. ‒ pp. 188-194. Chea, B. Trazodone: a review of its pharmacological properties and its off-label use in dogs and cats / B. Chea, M. Giorgi // Am J Anim Vet Sci. ‒ 2017. ‒ No. 12. ‒ pp. 188-194. Chincholkar, M. Analgesic mechanisms of gabapentinoids and effects in experimental pain models: a narrative review / Chincholkar M. // Br J Anaesth. ‒ 2018. ‒ No. 120(6). ‒ pp. 1315-1334. doi:10.1016/j.bja.2018.02.066. Chincholkar, M. Analgesic mechanisms of gabapentinoids and effects in experimental pain models: a narrative review / Chincholkar M. // Br J Anaesth. ‒ 2018. ‒ No. 120(6). ‒ pp. 1315-1334. doi:10.1016/j.bja.2018.02.066. Cisani, F. Acute Low Dose of Trazodone Recovers Glutamate Release Efficiency and mGlu2/3 Autoreceptor Impairments in the Spinal Cord of Rats Suffering From Chronic Sciatic Ligation / F. Cisani, A. Roggeri, G. Olivero, et al. // Front Pharmacol. ‒ 2020. ‒ No. 11. ‒ pp. 1108. doi:10.3389/fphar.2020.01108. Cisani, F. Acute Low Dose of Trazodone Recovers Glutamate Release Efficiency and mGlu2/3 Autoreceptor Impairments in the Spinal Cord of Rats Suffering From Chronic Sciatic Ligation / F. Cisani, A. Roggeri, G. Olivero, et al. // Front Pharmacol. ‒ 2020. ‒ No. 11. ‒ pp. 1108. doi:10.3389/fphar.2020.01108. Colvonen, P.J. Recent Advancements in Treating Sleep Disorders in Co-Occurring PTSD / P.J. Colvonen, L.D. Straus, C. Stepnowsky, M.J. McCarthy, L.A. Goldstein, S.B. Norman // Curr Psychiatry Rep. ‒ 2018. ‒ No. 20(7). ‒ pp. 48. Published 2018 Jun 21. doi:10.1007/s11920-018-0916-9. Colvonen, P.J. Recent Advancements in Treating Sleep Disorders in Co-Occurring PTSD / P.J. Colvonen, L.D. Straus, C. Stepnowsky, M.J. McCarthy, L.A. Goldstein, S.B. Norman // Curr Psychiatry Rep. ‒ 2018. ‒ No. 20(7). ‒ pp. 48. Published 2018 Jun 21. doi:10.1007/s11920-018-0916-9. Crociolli, G.C. Gabapentin as an adjuvant for postoperative pain management in dogs undergoing mastectomy / G.C. Crociolli, R.N. Cassu, R.C. Barbero, T.L. Rocha, D.R. Gomes, G.M. Nicácio // J Vet Med Sci. ‒ 2015. ‒ No. 77(8). ‒ pp. 1011-1015. doi:10.1292/jvms.14-0602. Crociolli, G.C. Gabapentin as an adjuvant for postoperative pain management in dogs undergoing mastectomy / G.C. Crociolli, R.N. Cassu, R.C. Barbero, T.L. Rocha, D.R. Gomes, G.M. Nicácio // J Vet Med Sci. ‒ 2015. ‒ No. 77(8). ‒ pp. 1011-1015. doi:10.1292/jvms.14-0602. Della Rocca, G. Chronic Pain in Dogs and Cats: Is There Place for Dietary Intervention with Micro-Palmitoylethanolamide? / G. Della Rocca, D. Gamba // Animals (Basel). ‒ 2021. ‒ No. 11(4). ‒ pp. 952. doi:10.3390/ani11040952. Della Rocca, G. Chronic Pain in Dogs and Cats: Is There Place for Dietary Intervention with Micro-Palmitoylethanolamide? / G. Della Rocca, D. Gamba // Animals (Basel). ‒ 2021. ‒ No. 11(4). ‒ pp. 952. doi:10.3390/ani11040952. Di Cesare, F. Gabapentin: Clinical Use and Pharmacokinetics in Dogs, Cats, and Horses / F. Di Cesare, V. Negro, G. Ravasio, R. Villa, S. Draghi, P. Cagnardi // Animals (Basel). ‒ 2023. ‒ No. 13(12). ‒ pp. 2045. doi:10.3390/ani13122045. Di Cesare, F. Gabapentin: Clinical Use and Pharmacokinetics in Dogs, Cats, and Horses / F. Di Cesare, V. Negro, G. Ravasio, R. Villa, S. Draghi, P. Cagnardi // Animals (Basel). ‒ 2023. ‒ No. 13(12). ‒ pp. 2045. doi:10.3390/ani13122045. Dooley, D.J. Ca2+ channel alpha2delta ligands: novel modulators of neurotransmission / D.J. Dooley, C.P. Taylor, S. Donevan, D. Feltner // Trends Pharmacol Sci. // 2007. ‒ No. 28(2). ‒ pp. 75-82. doi:10.1016/j.tips.2006.12.006. Dooley, D.J. Ca2+ channel alpha2delta ligands: novel modulators of neurotransmission / D.J. Dooley, C.P. Taylor, S. Donevan, D. Feltner // Trends Pharmacol Sci. // 2007. ‒ No. 28(2). ‒ pp. 75-82. doi:10.1016/j.tips.2006.12.006. Edwards, R.R. Variability in conditioned pain modulation predicts response to NSAID treatment in patients with knee osteoarthritis / R.R. Edwards, A.J. Dolman, M.O. Martel, et al. // BMC Musculoskelet Disord. ‒ 2016. ‒ No. 17. ‒ pp. 284. doi:10.1186/s12891-016-1124-6. Edwards, R.R. Variability in conditioned pain modulation predicts response to NSAID treatment in patients with knee osteoarthritis / R.R. Edwards, A.J. Dolman, M.O. Martel, et al. // BMC Musculoskelet Disord. ‒ 2016. ‒ No. 17. ‒ pp. 284. doi:10.1186/s12891-016-1124-6. Epstein, M.A. Managing Chronic Pain in Dogs and Cats, Part 2: The Best of the Rest in the Management of Osteoarthritis / M.A. Epstein. [Электронный ресурс]. – URL: https://todaysveterinarypractice.com/wp-content/uploads/sites/4/2016/06/T1409F03.pdf (дата обращения 15.01.2025) Epstein, M.A. Managing Chronic Pain in Dogs and Cats, Part 2: The Best of the Rest in the Management of Osteoarthritis / M.A. Epstein. [Elektronnyy resurs]. – URL: https://todaysveterinarypractice.com/wp-content/uploads/sites/4/2016/06/T1409F03.pdf (data obrascheniya 15.01.2025) Erickson, A. A review of pre-appointment medications to reduce fear and anxiety in dogs and cats at veterinary visits / A. Erickson, K. Harbin, J. MacPherson, K. Rundle, K.L. Overall // Can Vet J. ‒ 2021. ‒ No. 62(9). ‒ pp. 952-960. Erickson, A. A review of pre-appointment medications to reduce fear and anxiety in dogs and cats at veterinary visits / A. Erickson, K. Harbin, J. MacPherson, K. Rundle, K.L. Overall // Can Vet J. ‒ 2021. ‒ No. 62(9). ‒ pp. 952-960. Ghanbari, R. Sustained Administration of Trazodone Enhances Serotonergic Neurotransmission: In Vivo Electrophysiological Study in the Rat Brain / R. Ghanbari, et al. / Journal of Pharmacology and Experimental Therapeutics. ‒ 2010. ‒ No. 335. ‒ pp. 197-206. Ghanbari, R. Sustained Administration of Trazodone Enhances Serotonergic Neurotransmission: In Vivo Electrophysiological Study in the Rat Brain / R. Ghanbari, et al. / Journal of Pharmacology and Experimental Therapeutics. ‒ 2010. ‒ No. 335. ‒ pp. 197-206. Garrone, B. Synergistic interaction between trazodone and gabapentin in rodent models of neuropathic pain / B. Garrone // PLoS One. ‒ 2021. ‒ No. 16(1). ‒ e0244649. Garrone, B. Synergistic interaction between trazodone and gabapentin in rodent models of neuropathic pain / B. Garrone // PLoS One. ‒ 2021. ‒ No. 16(1). ‒ e0244649. Garry, E.M. Varicella zoster virus induces neuropathic changes in rat dorsal root ganglia and behavioral reflex sensitisation that is attenuated by gabapentin or sodium channel blocking drugs / E.M. Garry, A. Delaney, H.A. Anderson, et al. // Pain. ‒ 2005. ‒ No. 118 (1-2). ‒ pp. 97-111. doi:10.1016/j.pain.2005.08.003. Garry, E.M. Varicella zoster virus induces neuropathic changes in rat dorsal root ganglia and behavioral reflex sensitisation that is attenuated by gabapentin or sodium channel blocking drugs / E.M. Garry, A. Delaney, H.A. Anderson, et al. // Pain. ‒ 2005. ‒ No. 118 (1-2). ‒ pp. 97-111. doi:10.1016/j.pain.2005.08.003. Gilron, I. Nortriptyline and gabapentin, alone and in combination for neuropathic pain: a double-blind, randomised controlled crossover trial / I. Gilron, J.M. Bailey, D. Tu, R.R. Holden, A.C. Jackson, R.L. Houlden // Lancet. ‒ 2009. ‒ No. 374(9697). ‒ pp, 1252-1261. doi:10.1016/S0140-6736(09)61081-3. Gilron, I. Nortriptyline and gabapentin, alone and in combination for neuropathic pain: a double-blind, randomised controlled crossover trial / I. Gilron, J.M. Bailey, D. Tu, R.R. Holden, A.C. Jackson, R.L. Houlden // Lancet. ‒ 2009. ‒ No. 374(9697). ‒ pp, 1252-1261. doi:10.1016/S0140-6736(09)61081-3. Gruen, M.E. AAHA Pain Management Guidelines for Dogs and Cats / M.E. Gruen, B.D.X. Lascelles, E. Colleran, et al. // J Am Anim Hosp Assoc. ‒ 2022. ‒ No. 58(2). ‒ pp. 55-76. doi:10.5326/JAAHA-MS-7292. Gruen, M.E. AAHA Pain Management Guidelines for Dogs and Cats / M.E. Gruen, B.D.X. Lascelles, E. Colleran, et al. // J Am Anim Hosp Assoc. ‒ 2022. ‒ No. 58(2). ‒ pp. 55-76. doi:10.5326/JAAHA-MS-7292. Gildea, E. Use of Bedinvetmab (Librela®) for Canine Osteoarthritis in France, Germany, Italy, Spain, and the UK: Quantitative Analysis of Veterinarian Satisfaction and Real-World Treatment Patterns / E. Gildea, C. North, K. Walker, F. Adriaens, B.D.X. Lascelles // Animals (Basel). ‒ 2024. ‒ No. 14(15). ‒ pp. 2231. doi:10.3390/ani14152231. Gildea, E. Use of Bedinvetmab (Librela®) for Canine Osteoarthritis in France, Germany, Italy, Spain, and the UK: Quantitative Analysis of Veterinarian Satisfaction and Real-World Treatment Patterns / E. Gildea, C. North, K. Walker, F. Adriaens, B.D.X. Lascelles // Animals (Basel). ‒ 2024. ‒ No. 14(15). ‒ pp. 2231. doi:10.3390/ani14152231. Govendir, M. Improving seizure control in dogs with refractory epilepsy using gabapentin as an adjunctive agent / M. Govendir, M. Perkins, R. Malik // Aust Vet J. ‒ 2005. ‒ No. 83(10). ‒ pp. 602-608. doi:10.1111/j.1751-0813.2005.tb13269.x. Govendir, M. Improving seizure control in dogs with refractory epilepsy using gabapentin as an adjunctive agent / M. Govendir, M. Perkins, R. Malik // Aust Vet J. ‒ 2005. ‒ No. 83(10). ‒ pp. 602-608. doi:10.1111/j.1751-0813.2005.tb13269.x. Grubb, T. Chronic neuropathic pain in veterinary patients / Grubb T. // Top Companion Anim Med. ‒ 2010. ‒ No. 25(1). ‒ pp. 45-52. doi:10.1053/j.tcam.2009.10.007. Grubb, T. Chronic neuropathic pain in veterinary patients / Grubb T. // Top Companion Anim Med. ‒ 2010. ‒ No. 25(1). ‒ pp. 45-52. doi:10.1053/j.tcam.2009.10.007. Guy, S. Anticonvulsant medication use for the management of pain following spinal cord injury: systematic review and effectiveness analysis / S. Guy, S. Mehta, L. Leff, R. Teasell, E. Loh // Spinal Cord. ‒ 2014. ‒ No. 52(2). ‒ pp. 89-96. doi:10.1038/sc.2013.146. Guy, S. Anticonvulsant medication use for the management of pain following spinal cord injury: systematic review and effectiveness analysis / S. Guy, S. Mehta, L. Leff, R. Teasell, E. Loh // Spinal Cord. ‒ 2014. ‒ No. 52(2). ‒ pp. 89-96. doi:10.1038/sc.2013.146. Heughan, C.E. The interaction between gabapentin and amitriptyline in the rat formalin test after systemic administration / C.E. Heughan, J. Sawynok // Anesth Analg. ‒ 2002. ‒ No. 94(4). ‒ pp. 975-980. doi:10.1097/00000539-200204000-00037. Heughan, C.E. The interaction between gabapentin and amitriptyline in the rat formalin test after systemic administration / C.E. Heughan, J. Sawynok // Anesth Analg. ‒ 2002. ‒ No. 94(4). ‒ pp. 975-980. doi:10.1097/00000539-200204000-00037. Khurana, R.C. Treatment of painful diabetic neuropathy with trazodone / RC. Khurana / JAMA. ‒ 1983. ‒ No. 250(11). ‒ pp. 1392. doi:10.1001/jama.1983.03340110016015. Khurana, R.C. Treatment of painful diabetic neuropathy with trazodone / RC. Khurana / JAMA. ‒ 1983. ‒ No. 250(11). ‒ pp. 1392. doi:10.1001/jama.1983.03340110016015. Kukanich, B. Pharmacokinetics of oral gabapentin in greyhound dogs / B. Kukanich, R.L. Cohen // Vet J. ‒ 2011. ‒ No. 187(1). ‒ pp. 133-135. doi:10.1016/j.tvjl.2009.09.022. Kukanich, B. Pharmacokinetics of oral gabapentin in greyhound dogs / B. Kukanich, R.L. Cohen // Vet J. ‒ 2011. ‒ No. 187(1). ‒ pp. 133-135. doi:10.1016/j.tvjl.2009.09.022. Kuner, R. Central mechanisms of pathological pain / R. Kuner // Nat Med. ‒ 2010. ‒ No. 16(11). ‒ pp. 1258-1266. doi:10.1038/nm.2231. Kuner, R. Central mechanisms of pathological pain / R. Kuner // Nat Med. ‒ 2010. ‒ No. 16(11). ‒ pp. 1258-1266. doi:10.1038/nm.2231. Liu, V.W.C. Antidepressants for the Treatment of Neuropathic Pain / V.W.C. Liu, L.W. Lam, H.F.K. Chiu // Hong Kong J Psychiatry. ‒ 2002. ‒ No. 12(4). ‒ pp. 23-27. Liu, V.W.C. Antidepressants for the Treatment of Neuropathic Pain / V.W.C. Liu, L.W. Lam, H.F.K. Chiu // Hong Kong J Psychiatry. ‒ 2002. ‒ No. 12(4). ‒ pp. 23-27. Lipone, P. Efficacy and Safety of Low Doses of Trazodone in Patients Affected by Painful Diabetic Neuropathy and Treated with Gabapentin: A Randomized Controlled Pilot Study / P. Lipone, E. Ehler, M. Nastaj, et al. // CNS Drugs. ‒ 2020. ‒ No. 34(11). ‒ pp. 1177-1189. doi:10.1007/s40263-020-00760-2. Lipone, P. Efficacy and Safety of Low Doses of Trazodone in Patients Affected by Painful Diabetic Neuropathy and Treated with Gabapentin: A Randomized Controlled Pilot Study / P. Lipone, E. Ehler, M. Nastaj, et al. // CNS Drugs. ‒ 2020. ‒ No. 34(11). ‒ pp. 1177-1189. doi:10.1007/s40263-020-00760-2. Malkani, R. How does chronic pain impact the lives of dogs: an investigation of factors that are associated with pain using the Animal Welfare Assessment Grid Front / R. Malkani, S. Paramasivam, S. Wolfensohn // Vet Sci. ‒ No. 2024. ‒ No. 11. ‒ pp. 1374858. doi:10.3389/fvets.2024.1374858. Malkani, R. How does chronic pain impact the lives of dogs: an investigation of factors that are associated with pain using the Animal Welfare Assessment Grid Front / R. Malkani, S. Paramasivam, S. Wolfensohn // Vet Sci. ‒ No. 2024. ‒ No. 11. ‒ pp. 1374858. doi:10.3389/fvets.2024.1374858. McPeake, K.J. The Canine Frustration Questionnaire-Development of a New Psychometric Tool for Measuring Frustration in Domestic Dogs (Canis familiaris) / K.J. McPeake, L.M. Collins, H. Zulch, D.S. Mills // Front Vet Sci. ‒ 2019. ‒ No. 6. ‒ pp. 152. doi:10.3389/fvets.2019.00152. McPeake, K.J. The Canine Frustration Questionnaire-Development of a New Psychometric Tool for Measuring Frustration in Domestic Dogs (Canis familiaris) / K.J. McPeake, L.M. Collins, H. Zulch, D.S. Mills // Front Vet Sci. ‒ 2019. ‒ No. 6. ‒ pp. 152. doi:10.3389/fvets.2019.00152. Ménigaux, C. Preoperative gabapentin decreases anxiety and improves early functional recovery from knee surgery / C. Ménigaux, F. Adam, B. Guignard, D.I. Sessler, M. Chauvin // Anesth Analg. ‒ 2005. ‒ No. 100(5). ‒ pp. 1394-1399. doi:10.1213/01.ANE.0000152010.74739.B8. Ménigaux, C. Preoperative gabapentin decreases anxiety and improves early functional recovery from knee surgery / C. Ménigaux, F. Adam, B. Guignard, D.I. Sessler, M. Chauvin // Anesth Analg. ‒ 2005. ‒ No. 100(5). ‒ pp. 1394-1399. doi:10.1213/01.ANE.0000152010.74739.B8. Michels, G.M. A prospective, randomized, double-blind, placebo-controlled multisite, parallel-group field study in dogs with osteoarthritis conducted in the United States of America evaluating bedinvetmab, a canine anti-nerve growth factor monoclonal antibody / G.M. Michels, N.A. Honsberger, R.R. Walters, S. Kira, J. Tena, D.M. Cleaver / Vet Anaesth Analg. ‒ 2023. ‒ No. 50(5). ‒ pp. 446-458. doi:10.1016/j.vaa.2023.06.003. Michels, G.M. A prospective, randomized, double-blind, placebo-controlled multisite, parallel-group field study in dogs with osteoarthritis conducted in the United States of America evaluating bedinvetmab, a canine anti-nerve growth factor monoclonal antibody / G.M. Michels, N.A. Honsberger, R.R. Walters, S. Kira, J. Tena, D.M. Cleaver / Vet Anaesth Analg. ‒ 2023. ‒ No. 50(5). ‒ pp. 446-458. doi:10.1016/j.vaa.2023.06.003. Monteiro, B.P. WSAVA guidelines for the recognition, assessment and treatment of pain / B.P. Monteiro, et al. // J Small Anim Pract. ‒ 2022. ‒ No. 64 (4). ‒ pp. 177–254. doi: 10.1111/jsap.13566. Monteiro, B.P. WSAVA guidelines for the recognition, assessment and treatment of pain / B.P. Monteiro, et al. // J Small Anim Pract. ‒ 2022. ‒ No. 64 (4). ‒ pp. 177–254. doi: 10.1111/jsap.13566. Moore, S.A. Managing Neuropathic Pain in Dogs / S.A. Moore // Front Vet Sci. ‒ 2016. ‒ No. 3. ‒ pp. 12. doi:10.3389/fvets.2016.00012. Moore, S.A. Managing Neuropathic Pain in Dogs / S.A. Moore // Front Vet Sci. ‒ 2016. ‒ No. 3. ‒ pp. 12. doi:10.3389/fvets.2016.00012. Okuda, K. Trazodone hydrochloride attenuates thermal hyperalgesia in a chronic constriction injury rat model / K. Okuda, T. Takanishi, K. Yoshimoto, S. Ueda // Eur J Anaesthesiol. ‒ 2003. ‒ No. 20(5). ‒ pp. 409-415. doi:10.1017/s0265021503000632. Okuda, K. Trazodone hydrochloride attenuates thermal hyperalgesia in a chronic constriction injury rat model / K. Okuda, T. Takanishi, K. Yoshimoto, S. Ueda // Eur J Anaesthesiol. ‒ 2003. ‒ No. 20(5). ‒ pp. 409-415. doi:10.1017/s0265021503000632. Olivero, G. 5-HT2A-mGlu2/3 receptor complex in rat spinal cord glutamatergic nerve endings: A 5-HT2A to mGlu2/3 signalling to amplify presynaptic mechanism of auto-control of glutamate exocytosis / G. Olivero, M. Grilli, M. Vergassola, et al. // Neuropharmacology. ‒ 2018. ‒ No. 133. ‒ pp. 429-439. doi:10.1016/j.neuropharm.2018.02.030. Olivero, G. 5-HT2A-mGlu2/3 receptor complex in rat spinal cord glutamatergic nerve endings: A 5-HT2A to mGlu2/3 signalling to amplify presynaptic mechanism of auto-control of glutamate exocytosis / G. Olivero, M. Grilli, M. Vergassola, et al. // Neuropharmacology. ‒ 2018. ‒ No. 133. ‒ pp. 429-439. doi:10.1016/j.neuropharm.2018.02.030. Platt, S.R. Treatment with gabapentin of 11 dogs with refractory idiopathic epilepsy / S.R. Platt, V. Adams, L.S. Garosi, et al. // Vet Rec. ‒ 2006. ‒ No. 159(26). ‒ pp. 881-884. Platt, S.R. Treatment with gabapentin of 11 dogs with refractory idiopathic epilepsy / S.R. Platt, V. Adams, L.S. Garosi, et al. // Vet Rec. ‒ 2006. ‒ No. 159(26). ‒ pp. 881-884. Ruel, H.L.M. Pain burden, sensory profile and inflammatory cytokines of dogs with naturally-occurring neuropathic pain treated with gabapentin alone or with meloxicam / H.L.M. Ruel, R. Watanabe, M.C. Evangelista, et al. // PLoS One. ‒ 2020. ‒ No. 15(11). ‒ pp. e0237121. doi:10.1371/journal.pone.0237121. Ruel, H.L.M. Pain burden, sensory profile and inflammatory cytokines of dogs with naturally-occurring neuropathic pain treated with gabapentin alone or with meloxicam / H.L.M. Ruel, R. Watanabe, M.C. Evangelista, et al. // PLoS One. ‒ 2020. ‒ No. 15(11). ‒ pp. e0237121. doi:10.1371/journal.pone.0237121. Stahl, S.M. Anticonvulsants as anxiolytics, part 2: Pregabalin and gabapentin as alpha(2)delta ligands at voltage-gated calcium channels / S.M. Stahl // J Clin Psychiatry. ‒ 2004. ‒ No. 65(4). ‒ pp. 460-461. doi:10.4088/jcp.v65n0401. Stahl, S.M. Anticonvulsants as anxiolytics, part 2: Pregabalin and gabapentin as alpha(2)delta ligands at voltage-gated calcium channels / S.M. Stahl // J Clin Psychiatry. ‒ 2004. ‒ No. 65(4). ‒ pp. 460-461. doi:10.4088/jcp.v65n0401. Stahl, S.M. Mechanism of action of trazodone: a multifunctional drug / S.M. Stahl // CNS Spectr. ‒ 2009. ‒ No. 14(10). ‒ pp. 536-546. doi:10.1017/s1092852900024020. Stahl, S.M. Mechanism of action of trazodone: a multifunctional drug / S.M. Stahl // CNS Spectr. ‒ 2009. ‒ No. 14(10). ‒ pp. 536-546. doi:10.1017/s1092852900024020. Stollar, O.O. Effects of a single dose of orally administered gabapentin in dogs during a veterinary visit: a double-blinded, placebo-controlled study / O.O. Stollar, G.E. Moore, A. Mukhopadhyay, W. Gwin, N. Ogata // J Am Vet Med Assoc. ‒ 2022. ‒ No. 260(9). ‒ pp. 1031-1040. doi:10.2460/javma.21.03.0167. Stollar, O.O. Effects of a single dose of orally administered gabapentin in dogs during a veterinary visit: a double-blinded, placebo-controlled study / O.O. Stollar, G.E. Moore, A. Mukhopadhyay, W. Gwin, N. Ogata // J Am Vet Med Assoc. ‒ 2022. ‒ No. 260(9). ‒ pp. 1031-1040. doi:10.2460/javma.21.03.0167. Taylor, R. The utility of somatic items in the assessment of depression in patients with chronic pain: a comparison of the Zung Self-Rating Depression Scale and the Depression Anxiety Stress Scales in chronic pain and clinical and community samples / R. Taylor, P.F. Lovibond, M.K. Nicholas, C. Cayley, P.H. Wilson // Clin J Pain. ‒ 2005. ‒ No. 21(1). ‒ pp. 91-100. doi:10.1097/00002508-200501000-00011. Taylor, R. The utility of somatic items in the assessment of depression in patients with chronic pain: a comparison of the Zung Self-Rating Depression Scale and the Depression Anxiety Stress Scales in chronic pain and clinical and community samples / R. Taylor, P.F. Lovibond, M.K. Nicholas, C. Cayley, P.H. Wilson // Clin J Pain. ‒ 2005. ‒ No. 21(1). ‒ pp. 91-100. doi:10.1097/00002508-200501000-00011. Tesfaye, S. Efficacy and Safety of Trazodone and Gabapentin Fixed-Dose Combination in Patients Affected by Painful Diabetic Neuropathy: Randomized, Controlled, Dose-Finding Study / S. Tesfaye, P. Saravanan, E. Ehler, et al. // Pain Ther. ‒ 2024. ‒ No. 13(4). ‒ pp. 987-no. 1006. doi:10.1007/s40122-024-00624-3. Tesfaye, S. Efficacy and Safety of Trazodone and Gabapentin Fixed-Dose Combination in Patients Affected by Painful Diabetic Neuropathy: Randomized, Controlled, Dose-Finding Study / S. Tesfaye, P. Saravanan, E. Ehler, et al. // Pain Ther. ‒ 2024. ‒ No. 13(4). ‒ pp. 987-no. 1006. doi:10.1007/s40122-024-00624-3. Wagner, A.E. Clinical evaluation of perioperative administration of gabapentin as an adjunct for postoperative analgesia in dogs undergoing amputation of a forelimb / A.E. Wagner, P.M. Mich, S.R. Uhrig, P.W. Hellyer // J Am Vet Med Assoc. ‒ 2010. ‒ No. 236(7). ‒ pp. 751-756. doi:10.2460/javma.236.7.751. Wagner, A.E. Clinical evaluation of perioperative administration of gabapentin as an adjunct for postoperative analgesia in dogs undergoing amputation of a forelimb / A.E. Wagner, P.M. Mich, S.R. Uhrig, P.W. Hellyer // J Am Vet Med Assoc. ‒ 2010. ‒ No. 236(7). ‒ pp. 751-756. doi:10.2460/javma.236.7.751. Walsh, K. Chronic pain management in dogs and cats / K. Walsh // In Pract. ‒ 2016. ‒ No. 38. ‒ pp. 155-65. doi: 10.1136/inp.i1489 Walsh, K. Chronic pain management in dogs and cats / K. Walsh // In Pract. ‒ 2016. ‒ No. 38. ‒ pp. 155-65. doi: 10.1136/inp.i1489 Wallis, L.J. Utilising dog-computer interactions to provide mental stimulation in dogs especially during ageing / L.J. Wallis, F. Range, E. Kubinyi, D. Chapagain, J. Serra, L. Huber // ACI 2017 Improv Relat. ‒ 2017. ‒ No. 2017. ‒ pp. 1. doi:10.1145/3152130.3152146 Wallis, L.J. Utilising dog-computer interactions to provide mental stimulation in dogs especially during ageing / L.J. Wallis, F. Range, E. Kubinyi, D. Chapagain, J. Serra, L. Huber // ACI 2017 Improv Relat. ‒ 2017. ‒ No. 2017. ‒ pp. 1. doi:10.1145/3152130.3152146 Wiffen, P.J. WITHDRAWN: Gabapentin for acute and chronic pain / P.J. Wiffen, H.J. McQuay, J. Edwards, R.A .Moore // Cochrane Database Syst Rev. ‒ 2011. ‒ No. 2011(3). ‒ CD005452. doi:10.1002/14651858.CD005452.pub2. Wiffen, P.J. WITHDRAWN: Gabapentin for acute and chronic pain / P.J. Wiffen, H.J. McQuay, J. Edwards, R.A .Moore // Cochrane Database Syst Rev. ‒ 2011. ‒ No. 2011(3). ‒ CD005452. doi:10.1002/14651858.CD005452.pub2. Vasudevan, R. Alleviation of neuropathic pain by trazodone in rats / R. Vasudevan // Brazilian Journal of Pharmaceutical Sciences. ‒ 2022. ‒ No. 58. ‒ e19256. Vasudevan, R. Alleviation of neuropathic pain by trazodone in rats / R. Vasudevan // Brazilian Journal of Pharmaceutical Sciences. ‒ 2022. ‒ No. 58. ‒ e19256.