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Examination of effects, mechanisms of action and interactions of eslicarbazepine acetate and metformin in experimental pain models

dc.contributor.advisorTomić, Maja
dc.contributor.otherStepanović-Petrović, Radica
dc.contributor.otherMicov, Ana
dc.contributor.otherVučković, Sonja
dc.creatorPecikoza, Uroš
dc.date.accessioned2022-01-28T12:40:44Z
dc.date.available2022-01-28T12:40:44Z
dc.date.issued2021
dc.identifier.urihttp://eteze.bg.ac.rs/application/showtheses?thesesId=8244
dc.identifier.urihttps://fedorabg.bg.ac.rs/fedora/get/o:23972/bdef:Content/download
dc.identifier.urihttp://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=39014921
dc.identifier.urihttps://nardus.mpn.gov.rs/handle/123456789/18520
dc.identifier.urihttps://farfar.pharmacy.bg.ac.rs/handle/123456789/4037
dc.description.abstractBol je kompleksno senzorno iskustvo koje ima jasnu zaštitnu ulogu, ali pod određenim uslovima može da postane hronično stanje koje značajno narušava kvalitet života. Postojeći analgetici, iako nesumnjivo korisni u terapiji različitih bolnih stanja, neretko su nedovoljno efikasni ili bezbedni. Zato postoji potreba za razvojem novih ili otkrivanjem efikasnih kombinacija postojećih analgetika kako bi se poboljšala terapija bola.Ciljevi ovog rada su bili ispitivanje efekata, mehanizama dejstva i interakcija dva potencijalna alternativna analgetika, antiepileptika eslikarbazepin acetata (ESL) i antidijabetika metformina u modelima inflamatornog i neuropatskog bola.Efekti ESL i metformina su ispitani u modelima inflamatornog trigeminalnog, visceralnog i somatskog bola, kao i modelu bolne dijabetesne neuropatije. Mehanizmi dejstva ESL u modelu trigeminalnog bola su ispitani farmakološkim pristupom, korišćenjem antagonista receptora značajnih za modulaciju bola. Vrsta interakcije između ESL/metformina i analgetika u modelima inflamatornog i neuropatskog bola je utvrđena izobolografskom analizom.ESL i metformin su pokazali efikasnost u svim korišćenim modelima inflamatornog bola i u modelu bolne dijabetesne neuropatije. Utvrđeno je da ESL ublažava trigeminalni bol posredstvom serotoninskih 5-HT1B/1D, α2/β1-adrenergičkih, muskarinskih, CB1/CB2 kanabinoidnih i opioidnih receptora. ESL i metformin stupaju u aditivne ili sinergističke interakcije sa različitim analgeticima u modelima inflamatornog i neuropatskog bola.Efikasnost ESL i metformina u modelima bola bi mogla da ukaže na njihovu potencijalnu kliničku primenu kao analgetika. Dodatno, poznavanje mehanizama dejstva ESL može doprineti uspešnoj primeni ovog leka u terapiji bola. Na kraju, oba leka stupaju u povoljne interakcije sa postojećim analgeticima. Ovaj nalaz ukazuje na potencijalno bolju efikasnost i/ili bezbednost kombinovane u odnosu na monoterapiju, kao i koji analgetici bi mogli biti povoljan izbor za lečenje bola kod ljudi koji već primenjuju ESL/metformin zbog komorbiditeta.sr
dc.description.abstractPain is a complex sensory experience, which has a clear protective role, but under certain circumstances pain can become a chronic condition that significantly impairs the quality of life. Existing analgesics, although undoubtedly useful in the treatment of various painful conditions, are often insufficiently effective or safe. Therefore, there is a need to develop new drugs or to discover effective combinations of existing drugs in order to improve pain therapy.The objectives of this study were to investigate the effects, mechanisms of action, and interactions of two potential alternative analgesics, the antiepileptic eslicarbazepine acetate (ESL) and the antidiabetic metformin in models of inflammatory and neuropathic pain.The effects of ESL and metformin were examined in models of inflammatory trigeminal, visceral and somatic pain, as well as in a model of painful diabetic neuropathy. The mechanisms of action of ESL in the model of trigeminal pain were examined by a pharmacological approach, using antagonists of different receptors important for pain modulation. The type of interaction between ESL/metformin and analgesics in models of inflammatory and neuropathic pain was determined using isobolographic analysis.ESL and metformin were effective in all models of inflammatory pain that were used, as well as in the model of painful diabetic neuropathy. ESL was found to relieve trigeminal pain by activating serotonin 5-HT1B/1D, α2/β1-adrenergic, muscarinic, CB1/CB2 cannabinoid and opioid receptors. ESL and metformin interacted in an additive or synergistic manner with different analgesics in models of inflammatory and neuropathic pain.The efficacy of ESL and metformin in pain models may indicate their potential clinical application as analgesics. In addition, knowledge of the mechanisms of action of ESL may contribute to the successful use of this drug in the treatment of pain. Finally, both drugs interact favorably with existing analgesics. This finding indicates potentially better efficacy and/or safety of combination therapy compared to monotherapy, as well as which analgesics could be a favorable choice for the treatment of pain in people already using ESL/metformin due to comorbidities.en
dc.formatapplication/pdf
dc.languagesr
dc.publisherУниверзитет у Београду, Фармацеутски факултетsr
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/175045/RS//
dc.rightsopenAccessen
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.sourceУниверзитет у Београдуsr
dc.subjectalternativni analgetici, eslikarbazepin acetat, metformin, inflamatorni bol, neuropatski bol, trigeminalni bol, bolna dijabetesna neuropatija, modulacija bola, izobolograska analizasr
dc.subjectalternative analgesics, eslicarbazepine acetate, metformin, inflammatory pain, neuropathic pain, trigeminal pain, painful diabetic neuropathy, pain modulation, isobolographic analysisen
dc.titleIspitivanje efekata, mehanizama dejstva i interakcija eslikarbazepin acetata i metformina u eksperimentalnim modelima bolasr
dc.title.alternativeExamination of effects, mechanisms of action and interactions of eslicarbazepine acetate and metformin in experimental pain modelsen
dc.typedoctoralThesisen
dc.rights.licenseBY-NC-ND
dc.identifier.fulltexthttp://farfar.pharmacy.bg.ac.rs/bitstream/id/9414/Disertacija_11378.pdf
dc.identifier.fulltexthttp://farfar.pharmacy.bg.ac.rs/bitstream/id/9413/IzvestajKomisije11378.pdf
dc.identifier.rcubhttps://hdl.handle.net/21.15107/rcub_nardus_18520
dc.type.versionpublishedVersion


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