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dc.creatorMicov, Ana
dc.creatorTomić, Maja
dc.creatorPecikoza, Uroš
dc.creatorUgrešić, Nenad
dc.creatorStepanović-Petrović, Radica
dc.date.accessioned2019-09-02T11:47:55Z
dc.date.available2019-09-02T11:47:55Z
dc.date.issued2015
dc.identifier.issn1043-6618
dc.identifier.urihttp://farfar.pharmacy.bg.ac.rs/handle/123456789/2435
dc.description.abstractPainful diabetic neuropathy is difficult to treat. Single analgesics often have insufficient efficacy and poor tolerability. Combination therapy may therefore be of particular benefit, because it might provide optimal analgesia with fewer adverse effects. This study aimed to examine the type of interaction between levetiracetam, a novel anticonvulsant with analgesic properties, and commonly used analgesics (ibuprofen, aspirin and paracetamol) in a mouse model of painful diabetic neuropathy. Diabetes was induced in C57BL/6 mice with a single high dose of streptozotocin, applied intraperitoneally (150 mg/kg). Thermal (tail-flick test) and mechanical (electronic von Frey test) nociceptive thresholds were measured before and three weeks after diabetes induction. The antinociceptive effects of orally administered levetiracetam, analgesics, and their combinations were examined in diabetic mice that developed thermal/mechanical hypersensitivity. In combination experiments, the drugs were co-administered in fixed-dose fractions of single drug ED50 and the type of interaction was determined by isobolographic analysis. Levetiracetam (10-100 mg/kg), ibuprofen (2-50 mg/kg), aspirin (5-75 mg/kg), paracetamol (5-100 mg/kg), and levetiracetam-analgesic combinations produced significant, dose-dependent antinociceptive effects in diabetic mice in both tests. In the tail-flick test, isobolographic analysis revealed 15-, and 19-fold reduction of doses of both drugs in the combination of levetiracetam with aspirin/ibuprofen, and paracetamol, respectively. In the von Frey test, approximately 7- and 9-fold reduction of doses of both drugs was detected in levetiracetam-ibuprofen and levetiracetam-aspirin/levetiracetam-paracetamol combinations, respectively. These results show synergism between levetiracetam and ibuprofen/aspirin/paracetamol in a model of painful diabetic neuropathy and might provide a useful approach to the treatment of patients suffering from painful diabetic neuropathy.en
dc.publisherAcademic Press Ltd- Elsevier Science Ltd, London
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/175045/RS//
dc.rightsrestrictedAccess
dc.sourcePharmacological Research
dc.subjectLevetiracetamen
dc.subjectIbuprofenen
dc.subjectAspirinen
dc.subjectParacetamolen
dc.subjectSynergismen
dc.subjectDiabetic neuropathyen
dc.titleLevetiracetam synergises with common analgesics in producing antinociception in a mouse model of painful diabetic neuropathyen
dc.typearticle
dc.rights.licenseARR
dcterms.abstractСтепановић-Петровић, Радица; Томић, Маја; Мицов, Aна; Угрешић, Ненад; Пецикоза, Урош;
dc.citation.volume97
dc.citation.spage131
dc.citation.epage142
dc.citation.other97: 131-142
dc.citation.rankM21
dc.identifier.wos000357347600013
dc.identifier.doi10.1016/j.phrs.2015.04.014
dc.identifier.pmid25958352
dc.identifier.scopus2-s2.0-84930623649
dc.identifier.rcubconv_3339
dc.type.versionpublishedVersion


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