EXPERIMENTAL STUDY OF N-(γ-AMINOBUTYRYL)-1-AZA-4,7,10,13-TETRAOXACYCLOPENTADECANE HYDROCHLORIDE ANALGESIC ACTIVITY IN PAIN SYNDROMES OF DIFFERENT ETIOLOGY

Authors:

Abstract:

The pharmacotherapy of pain syndrome remains a significant and pressing medical issue. Therefore, scientists from various medical, pharmaceutical, and chemical specialties are working towards a solution. The study investigated the analgesic activity of N-(γ-aminobutyril)-1-aza-4,7,10,13-tetraoxacyclopentadecane hydrochloride (gabalgin), a new original compound, on laboratory animals. The severity and duration of the analgesic activity were evaluated using the “hot plate”, “tail flick”, “acetic writhing test”, and the neuropathic pain model, which was reproduced by ligation of the sciatic nerve in rats. The test compound was administered intraperitoneally at a dose of 3 mg/kg. The study found that gabalgin exhibits significant analgesic activity in all pain perception models, with comparable or superior strength to the comparison drugs ketorolac, gabapentin, and diclofenac. Additionally, gabalgin's antinociceptive effect lasts longer than diclofenac.

Keywords:

analgesic activity GABA derivatives crown ether neuropathic somatic thermal pain syndromes experiment rats mice

References:

1. Bohatskyi OV, Lukianenko MH, Voronina TO, ta in. vynakhidnyky N-(γ-aminobutyryl)-1-aza-4,7,10,13-tetraoksatsyklopentadekan hidrokhloryd, shcho maye antyamnestychnu, antyhipoksychnu ta protysudomnu aktyvnist. Patent 7121 Ukraina, MKY S 07 D 273/01. 1995 Cher 30. [in Ukrainian]
2. Holovenko MIa. Rol pokhidnykh 1,4-benzodiazepinu ta sporidnenykh spoluk u vyvchenni morfofunktsionalnoyi orhanizatsiyi neiroretseptoriv HAMK (ohliad literatury). Farmakolohiya ta likarska toksykolohiya. 2020; 14(6): 375–388. doi: https://doi.org/10.33250/14.06.375. [in Ukrainian]
3. Cohen SP, Vase L, Hooten WM. Chronic pain: an update on burden, best practices, and new advances. Lancet. 2021 May 29;397(10289):2082–2097. doi: 10.1016/S0140-6736(21)00393-7.
4. Cook DC, Goldstein PA. Non-canonical Molecular Targets for Novel Analgesics: Intracellular Calcium and HCN Channels. Curr Neuropharmacol. 2021 Oct 1;19(11):1937–1951. doi: https://doi.org/10.2174/1570159X19666210119153047.
5. Domenichiello AF, Ramsden CE. The silent epidemic of chronic pain in older adults. Prog Neuro-psychopharmacol Biol Psychiatry. 2019 Jul 13;93: 284–290. doi: https://doi.org/10.1016/j.pnpbp.2019.04.006.
6. Ferreira Kdos S, Speciali JG. Epidemiology of chronic pain in the office of a pain specialist neurologist. Arq Neuropsiquiatr. 2015 Jul;73(7):582–5. doi: 10.1590/0004-282X20150064.
7. Fisher E, Moore RA, Fogarty AE, Finn DP, Finnerup NB, Gilron I, et al. Cannabinoids, cannabis, and cannabis-based medicine for pain management: a systematic review of randomised controlled trials. Pain. 2021 Jul 1;162(1): 45–66. doi: 10.1097/j.pain.0000000000001929.
8. Golovenko NYa, Voloshchuk NI, Andronati SA, Taran IV, Reder АS, Pashynska ОS, et al. Аntinociception induced by a novel benzodiazepine receptor agonist and bradykinin receptor antagonist in rodent acute and chronic pain models. European Journal of Biomedical and Pharmaceutical sciences. 2018;5(12):79–88.
9. Laev SS, Salakhutdinov NF. New Small-molecule Analgesics. Med Chem. 2021;28(30):6234-6273. doi: https://doi.org/10.2174/0929867328666210614122444.
10. Mathieson S, Lin CC, Underwood M, Eldabe S. Pregabalin and gabapentin for pain. BMJ. 2020 Apr 28;369:1315. doi: https://doi.org/10.1136/bmj.m1315.
11. Mits V, Zachariou V. Modulation of pain, nociception, and analgesia by the brain reward center. Neuroscience. 2016 Dec 3; 338: 81–92. doi: https://doi.org/10.1016/j.neuroscience.2016.05.017.
12. Noguchi T, Umezaki Y, Takano R, Fujimoto T, Domon Y, Kubota K, et al. A novel [5.2.1]bicyclic amine is a potent analgesic without µ opioid activity. Bioorg Med Chem Lett (Bioorganic & Medicinal Chemistry Letters). 2021 Mar 15;36:127790. doi: https://doi.org/10.1016/j.bmcl.2021.127790.
13. Sydorenko A, Lutsenko R, Kniazkova I, Liakhovska N, Lutsenko O. Peculiarities of motor activity of rats in simulation pharmacological depressogenic states. Wiadomości Lekarskie. 2021 Sep; LXXIV;9(1):2105–2108. doi: 10.36740/WLek202109114
14. Vogel HG. Drug Discovery and Evaluation: Pharmacological Assays Berlin: Springer. 2008:1103-1106.
15. Xu A, Hilton E, Arkema R, Tintle NL, Helming LM. Epidemiology of chronic pain in Ukraine: Findings from the World Mental Health Survey PLoS One. 2019 Oct 17;14(10):e0224084. doi: 10.1371/journal.pone.0224084. eCollection 2019.

Publication:

«World of Medicine and Biology» Vol. 20 No. 87 (2024) , с. 187-191
УДК 616-001.1:615.9:547.466.3:547.6:599.323.4:612.08

DOI:

https://doi.org/10.26724/2079-8334-2024-1-87-187-191