title: Acute and chronic treatment with mianserin differentially affects the anticonvulsant activity of conventional antiepileptic drugs in the mouse maximal electroshock model.
abstract: BACKGROUND
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Experimental Neuropathophysiology Unit, Department of Pathophysiology, Lublin Medical University, Jaczewskiego 8, 20-090, Lublin, Poland. kinga.borowicz@am.lublin.pl
authors.forename: Kinga K
authors.initials: KK
authors.lastname: Borowicz
authors.forename: Monika
authors.initials: M
authors.lastname: Banach
authors.forename: Radosław
authors.initials: R
authors.lastname: Zarczuk
authors.forename: Dariusz
authors.initials: D
authors.lastname: Lukasik
authors.forename: Jarogniew J
authors.initials: JJ
authors.lastname: Luszczki
authors.forename: Stanislaw J
authors.initials: SJ
authors.lastname: Czuczwar
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000927:Anticonvulsants / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D018687:Antidepressive Agents, Second-Generation / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002220:Carbamazepine / Q000493:pharmacokinetics / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004357:Drug Synergism; D004597:Electroshock; D005455:Fluorescent Antibody Technique; D008297:Male; D008568:Memory / Q000187:drug effects; D008803:Mianserin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010634:Phenobarbital / Q000493:pharmacokinetics / Q000494:pharmacology; D010672:Phenytoin / Q000493:pharmacokinetics / Q000494:pharmacology; D012640:Seizures / Q000209:etiology / Q000517:prevention & control*; D014635:Valproic Acid / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D000927:Anticonvulsants; D018687:Antidepressive Agents, Second-Generation; D008803:Mianserin; D002220:Carbamazepine; D014635:Valproic Acid; D010672:Phenytoin; D010634:Phenobarbital