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dc.creatorTomić, Maja
dc.creatorVučković, Sonja M.
dc.creatorStepanović-Petrović, Radica
dc.creatorMicov, Ana
dc.creatorUgrešić, Nenad
dc.creatorProstran, Milica
dc.creatorBošković, Bogdan
dc.date.accessioned2019-09-02T11:21:26Z
dc.date.available2019-09-02T11:21:26Z
dc.date.issued2010
dc.identifier.issn0014-2999
dc.identifier.urihttps://farfar.pharmacy.bg.ac.rs/handle/123456789/1387
dc.description.abstractAntiepileptic and antidepressant drugs are the primary treatments for pain relief in diabetic neuropathy. Combination therapy is a valid approach in pain treatment, where a reduction of doses could reduce side effects and still achieve optimal analgesia. We examined the effects of two-drug combinations of gabapentin, oxcarbazepine, and amitriptyline on nociception in diabetic mice and aimed to determine the type of interaction between components. The nociceptive responses in normal and diabetic mice were assessed by the tail-flick test. The testing was performed before and three weeks after the diabetes induction with streptozotocin (150 mg/kg; i.p.), when the antinociceptive effects of gabapentin, oxcarbazepine, amitriptyline and their two-drug combinations were examined. Gabapentin (10-40 mg/kg; p.o.) and oxcarbazepine (20-80 mg/kg; p.o.) produced a significant, dose-dependent antinociception in diabetic mice while amitriptyline (5-60 mg/kg; p.o.) produced weak antinociceptive effect. In normal mice, neither of the drugs produced antinociception. Gabapentin and oxcarbazepine, co-administered in fixed-dose fractions of the ED(50) to diabetic mice, induced significant, dose-dependent antinociception. Isobolographic analysis revealed synergistic interaction. Oxcarbazepine (10-60mg/kg; p.o.)+amitriptyline (5mg/kg; p.o.) and gabapentin (10-30mg/kg: p.o.)+amitriptyline (5mg/kg; p.o.) combinations significantly and close-dependently reduced nociception in diabetic mice. Analysis of the log dose-response curves for oxcarbazepine or gabapentin in a presence of amitriptyline and oxcarbazepine or gabapentin applied alone, revealed a synergism in oxcarbazepine-amitriptyline and additivity in gabapentin-amitriptyline combination. These findings provide new information about the combination therapy of painful diabetic neuropathy and should be explored further in patients with diabetic neuropathy.en
dc.publisherElsevier Science BV, Amsterdam
dc.relationinfo:eu-repo/grantAgreement/MESTD/MPN2006-2010/145030/RS//
dc.rightsrestrictedAccess
dc.sourceEuropean Journal of Pharmacology
dc.subjectGabapentinen
dc.subjectOxcarbazepineen
dc.subjectAmitriptylineen
dc.subjectStreptozotocinen
dc.subjectDiabetic neuropathyen
dc.subjectSynergistic interactionen
dc.titleAnalysis of the antinociceptive interactions in two-drug combinations of gabapentin, oxcarbazepine and amitriptyline in streptozotocin-induced diabetic miceen
dc.typearticle
dc.rights.licenseARR
dcterms.abstractПростран, Милица; Томић, Маја; Мицов, Aна; Степановић-Петровић, Радица; Вучковић, Соња М.; Угрешић, Ненад; Бошковић, Богдан;
dc.citation.volume628
dc.citation.issue1-3
dc.citation.spage75
dc.citation.epage82
dc.citation.other628(1-3): 75-82
dc.citation.rankM22
dc.identifier.wos000274784500011
dc.identifier.doi10.1016/j.ejphar.2009.11.016
dc.identifier.pmid19917280
dc.identifier.scopus2-s2.0-73749084644
dc.type.versionpublishedVersion


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