Borowicz Kinga K, Furmanek-Karwowska Kamila, Sawicka Katarzyna, Luszczki Jarogniew J, Czuczwar Stanislaw J
Department of Pathophysiology, Lublin Medical University, Jaczewskiego 8, 20-090 Lublin, Poland.
Eur J Pharmacol. 2007 Jul 12;567(1-2):77-82. doi: 10.1016/j.ejphar.2007.03.015. Epub 2007 Mar 24.
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.
在小鼠最大电休克试验中研究了长期给予氟西汀与丙戊酸盐、卡马西平、苯妥英或苯巴比妥之间的相互作用。以高达20mg/kg的剂量给予氟西汀14天，未能影响惊厥阈值。然而，该药物（15mg和20mg）增强了丙戊酸盐、卡马西平及苯妥英的抗惊厥活性。当以20mg/kg应用时，它增强了苯巴比妥的保护作用。在烟囱试验（运动协调性）和被动回避任务（长期记忆）中评估，氟西汀、抗癫痫药物及其组合未产生明显的不良反应。长期应用氟西汀显著增加了丙戊酸盐、卡马西平、苯巴比妥及苯妥英的脑内浓度，表明药代动力学对观察到的药效学相互作用有影响。总之，长期用氟西汀治疗对传统抗癫痫药物的抗惊厥特性表现出一些有利作用，然而，这是由药代动力学相互作用所致。
