Effect of famotidine in combination with antiepileptic drugs on locomotor activity in mice

Histamine type 2 receptor antagonists are one of the most commonly used agents to treat peptic ulcer disease. Since patients with epilepsy may have many comorbidities, the aim of this study was to investigate the influence of one of the strongest second generation histamine type 2 receptor antagonist, famotidine, on the exploratory and spontaneous activity in mice after 1 or 7 days treatment. Additionally, the interaction between famotidine and antiepileptics: carbamazepine, phenytoin, phenobarbital or valproate and their effect on animals activity was also evaluated. Locomotor activity was monitored electronically using a Digiscan analyzer in relation to ambulatory and rearing activities, as well as total distance travelled by animals during 15 minute periods. Results of our study indicate that famotidine administered alone did not modulate three variables of exploratory motor activity (horizontal activity, total distance and vertical activity) in mice. On the other hand, famotidine co-administered with valproate (1 day) or phenobarbital (1 day or 7 days) worsened vertical activity in mice in exploratory time. Similarly, impairment in horizontal activity in mice was observed when famotidine was given with phenobarbital (1 or 7 days). An increase in total distance in mice after famotidine alone or in combination with tested antiepileptic drugs was also shown. Moreover, famotidine alone or together with antiepileptic agents significantly impaired spontaneous locomotor activity in mice. The presented results show that famotidine administration to patients with epilepsy should be considered as potentially hazardous.