Levetiracetam synergizes with gabapentin, pregabalin, duloxetine and selected antioxidants in a mouse diabetic painful neuropathy model
Abstract
Rationale We have reported that levetiracetam, a novel anticonvulsant with analgesic properties, synergizes with ibuprofen/aspirin/paracetamol in a model of diabetic painful neuropathy (DPN). Most guidelines recommend gabapentin, pregabalin, and duloxetine as first-or second-line agents for DPN. Objective We examined the effects of combination treatment of first-/second-line analgesics with levetiracetam in a model of DPN. Additionally, the levetiracetam's combinations with antioxidants, low dose of aspirin, coenzyme Q10, or alpha-lipoic acid were evaluated. Methods Diabetes was induced in C57BL/6 mice with a single high dose of streptozotocin. The antinociceptive effects of orally administered levetiracetam, gabapentin, pregabalin, duloxetine (acute treatment) and aspirin, coenzyme Q10, and alpha-lipoic acid (preventive 7-day treatment), as well as combinations of levetiracetam with individual drugs were examined in the tail-flick test. In combination experiments, the drugs were coadm...inistered in fixed-dose fractions of single-drug ED50; the type of interaction was determined by isobolographic analysis. Results About 60-, 32-, 30-, 26-, 18-, and 6-fold reductions of doses of both drugs in levetiracetam combinations with pregabalin, gabapentin, coenzyme Q10, aspirin, duloxetine, and alpha-lipoic acid, respectively, were detected. Conclusions Combinations of levetiracetam with gabapentin/pregabalin/duloxetine that target different mechanisms/sites of action involved in DPN, as well as combinations of levetiracetam and low-dose aspirin/coenzyme Q10/alpha-lipoic acid that target underlying causes of DPN, produce marked synergistic interactions in reducing nociception in diabetic mice. This suggests that these combination treatments might be of great benefit for diabetic patients and should be explored further in clinical trials.
Source:
QSAR & Combinatorial Science, 2017, 234, 11, 1781-1794Publisher:
- Springer, New York
Funding / projects:
DOI: 10.1007/s00213-017-4583-z
ISSN: 0033-3158
PubMed: 28332005
WoS: 000401631600013
Scopus: 2-s2.0-85015930895
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PharmacyTY - JOUR AU - Stepanović-Petrović, Radica AU - Micov, Ana AU - Tomić, Maja AU - Pecikoza, Uroš PY - 2017 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3023 AB - Rationale We have reported that levetiracetam, a novel anticonvulsant with analgesic properties, synergizes with ibuprofen/aspirin/paracetamol in a model of diabetic painful neuropathy (DPN). Most guidelines recommend gabapentin, pregabalin, and duloxetine as first-or second-line agents for DPN. Objective We examined the effects of combination treatment of first-/second-line analgesics with levetiracetam in a model of DPN. Additionally, the levetiracetam's combinations with antioxidants, low dose of aspirin, coenzyme Q10, or alpha-lipoic acid were evaluated. Methods Diabetes was induced in C57BL/6 mice with a single high dose of streptozotocin. The antinociceptive effects of orally administered levetiracetam, gabapentin, pregabalin, duloxetine (acute treatment) and aspirin, coenzyme Q10, and alpha-lipoic acid (preventive 7-day treatment), as well as combinations of levetiracetam with individual drugs were examined in the tail-flick test. In combination experiments, the drugs were coadministered in fixed-dose fractions of single-drug ED50; the type of interaction was determined by isobolographic analysis. Results About 60-, 32-, 30-, 26-, 18-, and 6-fold reductions of doses of both drugs in levetiracetam combinations with pregabalin, gabapentin, coenzyme Q10, aspirin, duloxetine, and alpha-lipoic acid, respectively, were detected. Conclusions Combinations of levetiracetam with gabapentin/pregabalin/duloxetine that target different mechanisms/sites of action involved in DPN, as well as combinations of levetiracetam and low-dose aspirin/coenzyme Q10/alpha-lipoic acid that target underlying causes of DPN, produce marked synergistic interactions in reducing nociception in diabetic mice. This suggests that these combination treatments might be of great benefit for diabetic patients and should be explored further in clinical trials. PB - Springer, New York T2 - QSAR & Combinatorial Science T1 - Levetiracetam synergizes with gabapentin, pregabalin, duloxetine and selected antioxidants in a mouse diabetic painful neuropathy model VL - 234 IS - 11 SP - 1781 EP - 1794 DO - 10.1007/s00213-017-4583-z ER -
@article{ author = "Stepanović-Petrović, Radica and Micov, Ana and Tomić, Maja and Pecikoza, Uroš", year = "2017", abstract = "Rationale We have reported that levetiracetam, a novel anticonvulsant with analgesic properties, synergizes with ibuprofen/aspirin/paracetamol in a model of diabetic painful neuropathy (DPN). Most guidelines recommend gabapentin, pregabalin, and duloxetine as first-or second-line agents for DPN. Objective We examined the effects of combination treatment of first-/second-line analgesics with levetiracetam in a model of DPN. Additionally, the levetiracetam's combinations with antioxidants, low dose of aspirin, coenzyme Q10, or alpha-lipoic acid were evaluated. Methods Diabetes was induced in C57BL/6 mice with a single high dose of streptozotocin. The antinociceptive effects of orally administered levetiracetam, gabapentin, pregabalin, duloxetine (acute treatment) and aspirin, coenzyme Q10, and alpha-lipoic acid (preventive 7-day treatment), as well as combinations of levetiracetam with individual drugs were examined in the tail-flick test. In combination experiments, the drugs were coadministered in fixed-dose fractions of single-drug ED50; the type of interaction was determined by isobolographic analysis. Results About 60-, 32-, 30-, 26-, 18-, and 6-fold reductions of doses of both drugs in levetiracetam combinations with pregabalin, gabapentin, coenzyme Q10, aspirin, duloxetine, and alpha-lipoic acid, respectively, were detected. Conclusions Combinations of levetiracetam with gabapentin/pregabalin/duloxetine that target different mechanisms/sites of action involved in DPN, as well as combinations of levetiracetam and low-dose aspirin/coenzyme Q10/alpha-lipoic acid that target underlying causes of DPN, produce marked synergistic interactions in reducing nociception in diabetic mice. This suggests that these combination treatments might be of great benefit for diabetic patients and should be explored further in clinical trials.", publisher = "Springer, New York", journal = "QSAR & Combinatorial Science", title = "Levetiracetam synergizes with gabapentin, pregabalin, duloxetine and selected antioxidants in a mouse diabetic painful neuropathy model", volume = "234", number = "11", pages = "1781-1794", doi = "10.1007/s00213-017-4583-z" }
Stepanović-Petrović, R., Micov, A., Tomić, M.,& Pecikoza, U.. (2017). Levetiracetam synergizes with gabapentin, pregabalin, duloxetine and selected antioxidants in a mouse diabetic painful neuropathy model. in QSAR & Combinatorial Science Springer, New York., 234(11), 1781-1794. https://doi.org/10.1007/s00213-017-4583-z
Stepanović-Petrović R, Micov A, Tomić M, Pecikoza U. Levetiracetam synergizes with gabapentin, pregabalin, duloxetine and selected antioxidants in a mouse diabetic painful neuropathy model. in QSAR & Combinatorial Science. 2017;234(11):1781-1794. doi:10.1007/s00213-017-4583-z .
Stepanović-Petrović, Radica, Micov, Ana, Tomić, Maja, Pecikoza, Uroš, "Levetiracetam synergizes with gabapentin, pregabalin, duloxetine and selected antioxidants in a mouse diabetic painful neuropathy model" in QSAR & Combinatorial Science, 234, no. 11 (2017):1781-1794, https://doi.org/10.1007/s00213-017-4583-z . .