Abstract | RATIONALE: OBJECTIVE: 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 α- 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 α- 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/α- 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.
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Authors | Radica Stepanović-Petrović, Ana Micov, Maja Tomić, Uroš Pecikoza |
Journal | Psychopharmacology
(Psychopharmacology (Berl))
Vol. 234
Issue 11
Pg. 1781-1794
(Jun 2017)
ISSN: 1432-2072 [Electronic] Germany |
PMID | 28332005
(Publication Type: Journal Article)
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Chemical References |
- Amines
- Analgesics
- Anticonvulsants
- Antioxidants
- Cyclohexanecarboxylic Acids
- Levetiracetam
- Pregabalin
- gamma-Aminobutyric Acid
- Gabapentin
- Duloxetine Hydrochloride
- Piracetam
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Topics |
- Amines
(administration & dosage)
- Analgesics
(administration & dosage)
- Animals
- Anticonvulsants
(administration & dosage)
- Antioxidants
(administration & dosage)
- Cyclohexanecarboxylic Acids
(administration & dosage)
- Diabetes Mellitus, Experimental
(blood, drug therapy, pathology)
- Diabetic Neuropathies
(blood, drug therapy, pathology)
- Disease Models, Animal
- Dose-Response Relationship, Drug
- Drug Synergism
- Duloxetine Hydrochloride
(administration & dosage)
- Gabapentin
- Levetiracetam
- Male
- Mice
- Mice, Inbred C57BL
- Piracetam
(administration & dosage, analogs & derivatives)
- Pregabalin
(administration & dosage)
- gamma-Aminobutyric Acid
(administration & dosage)
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