Acute and chronic treatment with mianserin differentially affects the anticonvulsant activity of conventional antiepileptic drugs in the mouse maximal electroshock model |
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Authors: | Kinga K Borowicz Monika Banach Rados?aw Zarczuk Dariusz Lukasik Jarogniew J Luszczki Stanislaw J Czuczwar |
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Institution: | (1) Experimental Neuropathophysiology Unit, Department of Pathophysiology, Lublin Medical University, Jaczewskiego 8, 20-090 Lublin, Poland;(2) Department of Physiopathology, Institute of Agricultural Medicine, Jaczewskiego 8, 20-090 Lublin, Poland |
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Abstract: | Rationale Epilepsy often coexists with depression. Therefore, the probability of simultaneous treatment with antiepileptics and antidepressants
and the possibility of interactions between them are relatively high.
Objective The effects of acute and chronic administration of mianserin on the protective activity of valproate (VPA), carbamazepine,
phenytoin, and phenobarbital were evaluated in the maximal electroshock in mice.
Materials and methods Animals were subjected to electroconvulsions. Undesired effects were evaluated in the chimney test (motor impairment) and
passive-avoidance task (memory deficit). Brain concentrations of antiepileptic drugs were assessed by immunofluorescence.
Results When given acutely, mianserin (at doses greater than or equal to 20 mg/kg) significantly raised the electroconvulsive threshold.
The antidepressant, at the subanticonvulsant doses, enhanced the anticonvulsant action of carbamazepine, phenytoin, and VPA.
Mianserin administered chronically at 30 mg/kg significantly decreased the electroconvulsive threshold. In contrast to acute
treatment, the antidepressant at subeffective doses diminished the anticonvulsant activity of VPA and phenytoin. Mianserin
given either acutely or chronically did not affect the brain concentrations of antiepileptic drugs, so a pharmacokinetic contribution
to the observed interactions is not probable.
Acute and chronic treatment with mianserin and its combinations with antiepileptic drugs did not impair either motor coordination
or long-term memory.
Conclusion Although acute application of mianserin may potentiate the anticonvulsant action of some antiepileptics, its chronic administration
can lead to the opposite effect. Therefore, as far as the presented results can be transferred to clinical conditions, the
antidepressant therapy with mianserin should be limited or even avoided in epileptic patients. |
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Keywords: | Mianserin Antiepileptic drugs Electroshock maximal Pharmacokinetic interaction |
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