Influence of ketotifen and conventional antiepileptic drugs on the exploratory and spontaneous locomotor activity in mice

Drug interactions are major problems in polytherapy, especially in epilepsy, and inappropriate drug selection may result in increased frequency of seizures.

In this study, the influence of histamine type 1 (H₁) receptor antagonist ketotifen and four chosen antiepileptic drugs (AEDs) on mice activity was examined. We evaluated three parameters of locomotor activity in mice: horizontal total activity with total distance and vertical activity, as well as animal spontaneous activity. Experiments were divided into two 15-minutes studies. During the first 15 minutes, we examined exploratory activity in mice; in the second period, spontaneous activity was tested. In the experiment, Ketotifen or vehicle were administered once or for 7 days daily, whereas AEDs were given only once before test performance.

Our results show that ketotifen given alone once or for 7 days significantly increased exploratory locomotor activity in mice without affecting their spontaneous activity. However, in combination with AEDs, ketotifen given once or for 7 days differently affected spontaneous and locomotor activity in mice. Our study indicates that the combination of ketotifen with AEDs needs special attention in pharmacotherapy of epilepsy.