FarFaR - Pharmacy Repository
University of Belgrade, Faculty of Pharmacy
    • English
    • Српски
    • Српски (Serbia)
  • English 
    • English
    • Serbian (Cyrilic)
    • Serbian (Latin)
  • Login
View Item 
  •   FarFaR
  • Pharmacy
  • Radovi istraživača / Researchers’ publications
  • View Item
  •   FarFaR
  • Pharmacy
  • Radovi istraživača / Researchers’ publications
  • View Item
JavaScript is disabled for your browser. Some features of this site may not work without it.

Analysis of the antinociceptive interactions in two-drug combinations of gabapentin, oxcarbazepine and amitriptyline in streptozotocin-induced diabetic mice

Authorized Users Only
2010
Authors
Tomić, Maja
Vučković, Sonja M.
Stepanović-Petrović, Radica
Micov, Ana
Ugrešić, Nenad
Prostran, Milica
Bošković, Bogdan
Article (Published version)
Metadata
Show full item record
Abstract
Antiepileptic 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.

Keywords:
Gabapentin / Oxcarbazepine / Amitriptyline / Streptozotocin / Diabetic neuropathy / Synergistic interaction
Source:
European Journal of Pharmacology, 2010, 628, 1-3, 75-82
Publisher:
  • Elsevier Science BV, Amsterdam
Projects:
  • Ispitivanje mehanizma dejstva, interakcija i toksičnih efekata analgetika kao i vazoaktivnih supstanci (RS-145030)

DOI: 10.1016/j.ejphar.2009.11.016

ISSN: 0014-2999

PubMed: 19917280

WoS: 000274784500011

Scopus: 2-s2.0-73749084644
[ Google Scholar ]
20
17
URI
http://farfar.pharmacy.bg.ac.rs/handle/123456789/1387
Collections
  • Radovi istraživača / Researchers’ publications
Institution
Pharmacy

DSpace software copyright © 2002-2015  DuraSpace
About FarFaR - Pharmacy Repository | Send Feedback

OpenAIRERCUB
 

 

All of DSpaceInstitutionsAuthorsTitlesSubjectsThis institutionAuthorsTitlesSubjects

Statistics

View Usage Statistics

DSpace software copyright © 2002-2015  DuraSpace
About FarFaR - Pharmacy Repository | Send Feedback

OpenAIRERCUB