Effect of acute and chronic tianeptine on the action of classical antiepileptics in the mouse maximal electroshock model
Kinga K. Borowicz
1, Monika Banach
1, Barbara Piskorska
1, Stanis³aw J. Czuczwar
1,21Independent Unit of Experimental Neuropathophysiology, Department of Pathophysiology, Medical University, Jaczewskiego 8, PL-20-954 Lublin, Poland
2Department of Physiopathology, Institute of Agricultural Medicine, Jaczewskiego 2, PL-20-950 Lublin, Poland Correspondence: Kinga Borowicz, e-mail: kinga.borowicz@umlub.pl
Abstract:
Background: The aim of the study was to analyze the influence of acute and chronic treatment with tianeptine, an antidepressant se- lectively accelerating presynaptic serotonin reuptake, on the protective activity of classical antiepileptic drugs in the maximal elec- troshock test in mice.
Methods: Electroconvulsions were produced by means of an alternating current (50 Hz, 25 mA, 0.2 s) delivered via ear-clip electrodes. Motor impairment and long-term memory deficits in animals were quantified in the chimney test and in the passive- avoidance task, respectively. Brain concentrations of antiepileptic drugs were measured by fluorescence polarization immunoassay.
Results: Acute and chronic treatment with tianeptine (25–50 mg/kg) did not affect the electroconvulsive threshold. Furthermore, tia- neptine applied in both acute and chronic protocols enhanced the anticonvulsant action of valproate and carbamazepine, but not that of phenytoin. Neither acute nor chronic tianeptine changed the brain concentrations of valproate, carbamazepine or phenytoin. On the other hand, both single and chronic administration of tianeptine diminished the brain concentration of phenobarbital. In spite of this pharmacokinetic interaction, the antidepressant enhanced the antielectroshock action of phenobarbital. In terms of adverse ef- fects, acute/chronic tianeptine (50 mg/kg) and its combinations with classic antiepileptic drugs did not impair motor performance or long-term memory in mice.
Conclusion: The obtained results justify the conclusion that tianeptine may be beneficial in the treatment of depressive disorders in the course of epilepsy.
Key words:
tianeptine, antiepileptic drugs, electroshock maximal, pharmacokinetic interaction
Pharmacological Reports, 2013, 65, 379388 379
Pharmacological Reports 2013, 65, 379388 ISSN 1734-1140
Copyright © 2013 by Institute of Pharmacology Polish Academy of Sciences