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dc.creatorTomić, Maja
dc.creatorMicov, Ana
dc.creatorStepanović-Petrović, Radica
dc.date.accessioned2019-09-02T11:33:48Z
dc.date.available2019-09-02T11:33:48Z
dc.date.issued2013
dc.identifier.issn1526-5900
dc.identifier.urihttp://farfar.pharmacy.bg.ac.rs/handle/123456789/1899
dc.description.abstractLevetiracetam is a novel anticonvulsant with antihyperalgesic efficacy in inflammatory pain. Nonsteroidal analgesics and caffeine, as analgesic adjuvant, are widely used against inflammatory pain. This study characterized the manner in which levetiracetam interacts with analgesics (ibuprofen, celecoxib, and paracetamol) and caffeine to suppress hyperalgesia in a model of localized inflammation. Rat paw inflammation was induced by intraplantar carrageenan (.1 mL, 1%). Hyperalgesia and antihyperalgesic effects of levetiracetam (orally), analgesics (orally), and caffeine (intraperitoneally) alone and 2-drug combinations of levetiracetam with analgesics or caffeine were examined by a modified paw pressure test. The type of interaction between components was determined by isobolographic analysis or by analysis of the log dose-response curves for drug combination and drugs alone. Levetiracetam (10-200 mg/kg), ibuprofen (12.5-100 mg/kg), celecoxib (3.75-30 mg/kg), paracetamol (50-200 mg/kg), caffeine (15-100 mg/kg), and 2-drug combinations of levetiracetam with analgesics/caffeine produced a significant, dose-dependent reduction of inflammatory hyperalgesia. Isobolographic analysis revealed that levetiracetam exerts a synergistic interaction with analgesics, with approximately 7-, 9-, and 11-fold reduction of doses of both drugs in combination of levetiracetam with paracetamol, celecoxib, and ibuprofen, respectively. Analysis of the log dose-response curves for levetiracetam (1-50 mg/kg) in the presence of caffeine (10 mg/kg) and levetiracetam applied alone also revealed a synergistic interaction. Levetiracetam's ED50 in the presence of caffeine was reduced approximately 11-fold. Perspective: The presented data suggest that 2-drug combinations of levetiracetam and nonsteroidal analgesics or caffeine could be useful in treatment of inflammatory pain. The efficacy and the adverse effects of those mixtures should be explored further in clinical settings.en
dc.publisherChurchill Livingstone, Edinburgh
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/175045/RS//
dc.rightsrestrictedAccess
dc.sourceJournal of Pain
dc.subjectLevetiracetamen
dc.subjectanalgesicsen
dc.subjectcaffeineen
dc.subjectsynergismen
dc.subjectinflammatory painen
dc.titleLevetiracetam Interacts Synergistically With Nonsteroidal Analgesics and Caffeine to Produce Antihyperalgesia in Ratsen
dc.typearticle
dc.rights.licenseARR
dcterms.abstractСтепановић-Петровић, Радица; Томић, Маја; Мицов, Aна;
dc.citation.volume14
dc.citation.issue11
dc.citation.spage1371
dc.citation.epage1382
dc.citation.other14(11): 1371-1382
dc.citation.rankM21
dc.identifier.wos000327047900011
dc.identifier.doi10.1016/j.jpain.2013.06.003
dc.identifier.pmid23954518
dc.identifier.scopus2-s2.0-84887026764
dc.identifier.rcubconv_2962
dc.type.versionpublishedVersion


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