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dc.creatorStepanović-Petrović, Radica
dc.creatorMicov, Ana
dc.creatorTomić, Maja
dc.creatorPecikoza, Uroš
dc.date.accessioned2019-09-02T12:02:55Z
dc.date.available2019-09-02T12:02:55Z
dc.date.issued2017
dc.identifier.issn0033-3158
dc.identifier.urihttp://farfar.pharmacy.bg.ac.rs/handle/123456789/3023
dc.description.abstractRationale We have reported that levetiracetam, a novel anticonvulsant with analgesic properties, synergizes with ibuprofen/aspirin/paracetamol in a model of diabetic painful neuropathy (DPN). Most guidelines recommend gabapentin, pregabalin, and duloxetine as first-or second-line agents for DPN. Objective We examined the effects of combination treatment of first-/second-line analgesics with levetiracetam in a model of DPN. Additionally, the levetiracetam's combinations with antioxidants, low dose of aspirin, coenzyme Q10, or alpha-lipoic acid were evaluated. Methods Diabetes was induced in C57BL/6 mice with a single high dose of streptozotocin. The antinociceptive effects of orally administered levetiracetam, gabapentin, pregabalin, duloxetine (acute treatment) and aspirin, coenzyme Q10, and alpha-lipoic acid (preventive 7-day treatment), as well as combinations of levetiracetam with individual drugs were examined in the tail-flick test. In combination experiments, the drugs were coadministered in fixed-dose fractions of single-drug ED50; the type of interaction was determined by isobolographic analysis. Results About 60-, 32-, 30-, 26-, 18-, and 6-fold reductions of doses of both drugs in levetiracetam combinations with pregabalin, gabapentin, coenzyme Q10, aspirin, duloxetine, and alpha-lipoic acid, respectively, were detected. Conclusions Combinations of levetiracetam with gabapentin/pregabalin/duloxetine that target different mechanisms/sites of action involved in DPN, as well as combinations of levetiracetam and low-dose aspirin/coenzyme Q10/alpha-lipoic acid that target underlying causes of DPN, produce marked synergistic interactions in reducing nociception in diabetic mice. This suggests that these combination treatments might be of great benefit for diabetic patients and should be explored further in clinical trials.en
dc.publisherSpringer, New York
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/175045/RS//
dc.rightsrestrictedAccess
dc.sourceQSAR & Combinatorial Science
dc.titleLevetiracetam synergizes with gabapentin, pregabalin, duloxetine and selected antioxidants in a mouse diabetic painful neuropathy modelen
dc.typearticle
dc.rights.licenseARR
dcterms.abstractМицов, Aна; Пецикоза, Урош; Томић, Маја; Степановић-Петровић, Радица;
dc.citation.volume234
dc.citation.issue11
dc.citation.spage1781
dc.citation.epage1794
dc.citation.other234(11): 1781-1794
dc.citation.rankM21
dc.identifier.wos000401631600013
dc.identifier.doi10.1007/s00213-017-4583-z
dc.identifier.pmid28332005
dc.identifier.scopus2-s2.0-85015930895
dc.identifier.rcubconv_3850
dc.type.versionpublishedVersion


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