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Levetiracetam synergises with common analgesics in producing antinociception in a mouse model of painful diabetic neuropathy

Authorized Users Only
2015
Authors
Micov, Ana
Tomić, Maja
Pecikoza, Uroš
Ugrešić, Nenad
Stepanović-Petrović, Radica
Article (Published version)
Metadata
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Abstract
Painful 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-a...dministered 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.

Keywords:
Levetiracetam / Ibuprofen / Aspirin / Paracetamol / Synergism / Diabetic neuropathy
Source:
Pharmacological Research, 2015, 97, 131-142
Publisher:
  • Academic Press Ltd- Elsevier Science Ltd, London
Projects:
  • Examination of mechanisms of action, toxicity and interactions of adjuvant analgesics (RS-175045)

DOI: 10.1016/j.phrs.2015.04.014

ISSN: 1043-6618

PubMed: 25958352

WoS: 000357347600013

Scopus: 2-s2.0-84930623649
[ Google Scholar ]
9
9
URI
http://farfar.pharmacy.bg.ac.rs/handle/123456789/2435
Collections
  • Radovi istraživača / Researchers’ publications
Institution
Pharmacy
TY  - JOUR
AU  - Micov, Ana
AU  - Tomić, Maja
AU  - Pecikoza, Uroš
AU  - Ugrešić, Nenad
AU  - Stepanović-Petrović, Radica
PY  - 2015
UR  - http://farfar.pharmacy.bg.ac.rs/handle/123456789/2435
AB  - Painful 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.
PB  - Academic Press Ltd- Elsevier Science Ltd, London
T2  - Pharmacological Research
T1  - Levetiracetam synergises with common analgesics in producing antinociception in a mouse model of painful diabetic neuropathy
VL  - 97
SP  - 131
EP  - 142
DO  - 10.1016/j.phrs.2015.04.014
ER  - 
@article{
author = "Micov, Ana and Tomić, Maja and Pecikoza, Uroš and Ugrešić, Nenad and Stepanović-Petrović, Radica",
year = "2015",
url = "http://farfar.pharmacy.bg.ac.rs/handle/123456789/2435",
abstract = "Painful 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.",
publisher = "Academic Press Ltd- Elsevier Science Ltd, London",
journal = "Pharmacological Research",
title = "Levetiracetam synergises with common analgesics in producing antinociception in a mouse model of painful diabetic neuropathy",
volume = "97",
pages = "131-142",
doi = "10.1016/j.phrs.2015.04.014"
}
Micov A, Tomić M, Pecikoza U, Ugrešić N, Stepanović-Petrović R. Levetiracetam synergises with common analgesics in producing antinociception in a mouse model of painful diabetic neuropathy. Pharmacological Research. 2015;97:131-142
Micov, A., Tomić, M., Pecikoza, U., Ugrešić, N.,& Stepanović-Petrović, R. (2015). Levetiracetam synergises with common analgesics in producing antinociception in a mouse model of painful diabetic neuropathy.
Pharmacological ResearchAcademic Press Ltd- Elsevier Science Ltd, London., 97, 131-142.
https://doi.org/10.1016/j.phrs.2015.04.014
Micov Ana, Tomić Maja, Pecikoza Uroš, Ugrešić Nenad, Stepanović-Petrović Radica, "Levetiracetam synergises with common analgesics in producing antinociception in a mouse model of painful diabetic neuropathy" 97 (2015):131-142,
https://doi.org/10.1016/j.phrs.2015.04.014 .

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