Chronically administered fluoxetine enhances the anticonvulsant activity of conventional antiepileptic drugs in the mouse maximal electroshock model.
Interactions between chronically administered fluoxetine and valproate, carbamazepine, phenytoin, or phenobarbital were studied in the maximal electroshock test in mice. Fluoxetine administered for 14 days at doses up to 20 mg/kg failed to affect the electroconvulsive threshold. Nevertheless the drug (at 15 and 20 mg) enhanced the anticonvulsant activity of valproate, carbamazepine, and phenytoin. When applied at 20 mg/kg, it potentiated the protective action of phenobarbital. Fluoxetine, antiepileptic drugs, and their combinations did not produce significant adverse effects evaluated in the chimney test (motor coordination) and passive-avoidance task (long-term memory). Chronically applied fluoxetine significantly increased the brain concentrations of valproate, carbamazepine, phenobarbital and phenytoin, indicating a pharmacokinetic contribution to the observed pharmacodynamic interactions. In conclusion, long-term treatment with fluoxetine exhibited some favorable effects on the anticonvulsant properties of conventional antiepileptic drugs, resulting, however, from pharmacokinetic interactions.
Borowicz
Kinga K
KK
Department of Pathophysiology, Lublin Medical University, Jaczewskiego 8, 20-090 Lublin, Poland. kinga.borowicz@am.lublin.pl
Furmanek-Karwowska
Kamila
K
Sawicka
Katarzyna
K
Luszczki
Jarogniew J
JJ
Czuczwar
Stanislaw J
SJ
D000818:Animals; D000927:Anticonvulsants / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D001362:Avoidance Learning / Q000187:drug effects; D001921:Brain / Q000378:metabolism; D002220:Carbamazepine / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D004347:Drug Interactions; D004357:Drug Synergism; D004597:Electroshock; D005473:Fluoxetine / Q000009:adverse effects / Q000494:pharmacology*; D008297:Male; D008568:Memory / Q000187:drug effects; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010634:Phenobarbital / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D010672:Phenytoin / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D012640:Seizures / Q000188:drug therapy* / Q000209:etiology; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000494:pharmacology*; D014635:Valproic Acid / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology
D000927:Anticonvulsants; D002220:Carbamazepine; D005473:Fluoxetine; D010634:Phenobarbital; D010672:Phenytoin; D017367:Selective Serotonin Reuptake Inhibitors; D014635:Valproic Acid