Analysis of the antinociceptive interactions in two-drug combinations of gabapentin, oxcarbazepine and amitriptyline in streptozotocin-induced diabetic mice
Само за регистроване кориснике
2010
Аутори
Tomić, MajaVučković, Sonja M.
Stepanović-Petrović, Radica
Micov, Ana
Ugrešić, Nenad
Prostran, Milica
Bošković, Bogdan
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
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.
Кључне речи:
Gabapentin / Oxcarbazepine / Amitriptyline / Streptozotocin / Diabetic neuropathy / Synergistic interactionИзвор:
European Journal of Pharmacology, 2010, 628, 1-3, 75-82Издавач:
- Elsevier Science BV, Amsterdam
Финансирање / пројекти:
- Испитивање механизма дејства, интеракција и токсичних ефеката аналгетика као и вазоактивних супстанци (RS-MESTD-MPN2006-2010-145030)
DOI: 10.1016/j.ejphar.2009.11.016
ISSN: 0014-2999
PubMed: 19917280
WoS: 000274784500011
Scopus: 2-s2.0-73749084644
Институција/група
PharmacyTY - JOUR AU - Tomić, Maja AU - Vučković, Sonja M. AU - Stepanović-Petrović, Radica AU - Micov, Ana AU - Ugrešić, Nenad AU - Prostran, Milica AU - Bošković, Bogdan PY - 2010 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1387 AB - 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. PB - Elsevier Science BV, Amsterdam T2 - European Journal of Pharmacology T1 - Analysis of the antinociceptive interactions in two-drug combinations of gabapentin, oxcarbazepine and amitriptyline in streptozotocin-induced diabetic mice VL - 628 IS - 1-3 SP - 75 EP - 82 DO - 10.1016/j.ejphar.2009.11.016 ER -
@article{ author = "Tomić, Maja and Vučković, Sonja M. and Stepanović-Petrović, Radica and Micov, Ana and Ugrešić, Nenad and Prostran, Milica and Bošković, Bogdan", year = "2010", 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.", publisher = "Elsevier Science BV, Amsterdam", journal = "European Journal of Pharmacology", title = "Analysis of the antinociceptive interactions in two-drug combinations of gabapentin, oxcarbazepine and amitriptyline in streptozotocin-induced diabetic mice", volume = "628", number = "1-3", pages = "75-82", doi = "10.1016/j.ejphar.2009.11.016" }
Tomić, M., Vučković, S. M., Stepanović-Petrović, R., Micov, A., Ugrešić, N., Prostran, M.,& Bošković, B.. (2010). Analysis of the antinociceptive interactions in two-drug combinations of gabapentin, oxcarbazepine and amitriptyline in streptozotocin-induced diabetic mice. in European Journal of Pharmacology Elsevier Science BV, Amsterdam., 628(1-3), 75-82. https://doi.org/10.1016/j.ejphar.2009.11.016
Tomić M, Vučković SM, Stepanović-Petrović R, Micov A, Ugrešić N, Prostran M, Bošković B. Analysis of the antinociceptive interactions in two-drug combinations of gabapentin, oxcarbazepine and amitriptyline in streptozotocin-induced diabetic mice. in European Journal of Pharmacology. 2010;628(1-3):75-82. doi:10.1016/j.ejphar.2009.11.016 .
Tomić, Maja, Vučković, Sonja M., Stepanović-Petrović, Radica, Micov, Ana, Ugrešić, Nenad, Prostran, Milica, Bošković, Bogdan, "Analysis of the antinociceptive interactions in two-drug combinations of gabapentin, oxcarbazepine and amitriptyline in streptozotocin-induced diabetic mice" in European Journal of Pharmacology, 628, no. 1-3 (2010):75-82, https://doi.org/10.1016/j.ejphar.2009.11.016 . .