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The Thai Journal of Pharmaceutical Sciences

Abstract

Background: Some antiepileptic drugs for instance levetiracetam cause depression in patients. Vitamin B6 is a cofactor involved in the neurotransmitter synthesis. α-Lipoic acid (ALA) is a mitochondrial cofactor that can prevent neuronal damage. The aim of this study was to evaluate the effectiveness of B6 and ALA for preventing levetiracetam depression in mice. Methods: Male NMRI mice (weighing 25 ± 3 g) were used. Levetiracetam (20 mg/kg), and pretreatments with ALA (20, 40 mg/kg), Vitamin B6 (100 mg/kg), or imipramine (10 mg/kg) as the control positive were all administered intraperitonealy for 14 consecutive days. The locomotor test and forced swimming test (FST) were performed on days 7 and 15 on same groups of animals, novelty suppressed feeding test (NSFT) was tested on day 16. Results: Immobility time in FST increased following levetiracetam administration (day 7, 166 ± 5.63s vs. control 135 ± 9.9s, P = 0.020; day15, 188 ± 6.45s vs. control 150 ± 9.55s, P = 0.0326). Pre-treatment with B6 significantly reduced the immobility time during FST (day 7, 109 ± 16.4s, P < 0.001; day 15, 124 ± 12s, P < 0.001 vs. levetiracetam alone), these changes were similar to imipramine, treatments did not change the locomotor activity. However, following ALA pre-treatment, the locomotor activity declined and neither of ALA doses reduced immobility time during FST. During NSFT, pre-treatment with B6, and ALA similar to imipramine decreased latency; B6 and ALA 20 mg/kg increased food intake compared to levetiracetam alone. Conclusion: While B6 pretreatment clearly prevented depressive-like behavior induced by levetiracetam, ALA 20 mg/kg showed antidepressant-like effect only in NSFT. Supplements are recommended for further evaluation to prevent depression comorbidity of antiepileptic drugs.

Publisher

Faculty of Pharmaceutical Sciences, Chulalongkorn University

First Page

682

Last Page

687

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