Levetiracetam synergises with common analgesics in producing antinociception in a mouse model of painful diabetic neuropathy
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 neuropathySource:
Pharmacological Research, 2015, 97, 131-142Publisher:
- Academic Press Ltd- Elsevier Science Ltd, London
Funding / projects:
- Examination of mechanisms of action, toxicity and interactions of adjuvant analgesics (RS-MESTD-Basic Research (BR or ON)-175045)
DOI: 10.1016/j.phrs.2015.04.014
ISSN: 1043-6618
PubMed: 25958352
WoS: 000357347600013
Scopus: 2-s2.0-84930623649
Collections
Institution/Community
PharmacyTY - JOUR AU - Micov, Ana AU - Tomić, Maja AU - Pecikoza, Uroš AU - Ugrešić, Nenad AU - Stepanović-Petrović, Radica PY - 2015 UR - https://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", 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.. (2015). Levetiracetam synergises with common analgesics in producing antinociception in a mouse model of painful diabetic neuropathy. in Pharmacological Research Academic Press Ltd- Elsevier Science Ltd, London., 97, 131-142. https://doi.org/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. in Pharmacological Research. 2015;97:131-142. doi: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" in Pharmacological Research, 97 (2015):131-142, https://doi.org/10.1016/j.phrs.2015.04.014 . .