Effect of lamotrigine alone or in combination with conventional antiepileptic drugs on locomotor activity in mice

OBJECTIVE: To evaluate the acute adverse effects with respect to exploratory and spontaneous locomotor activity of mice produced by lamotrigine (LTG) alone or in combination with conventional antiepileptic drugs (AEDs) such as valproate, diphenylhydantoin, carbamazepine and phenobarbital.
MATERIAL AND METHODS: Adult male mice were given an i.p. injection of LTG alone or in combination with conventional AEDs. When the maximum anticonvulsant activity of AEDs was at its peak, the exploratory and spontaneous locomotor activity of animals was electronically monitored. Three parameters (ambulatory activity, rearing activity and total distance traveled by animals) as indicators of the locomotor activity of the animals tested were electronically evaluated by means of the locomotor monitor system.
RESULTS: The combination of LTG and valproate was devoid of any adverse effects on the locomotor activity. In contrast, the combination of LTG and carbamazepine drastically reduced the exploratory and spontaneous locomotor activity of animals in all analyzed parameters. Likewise, diphenylhydantoin combined with LTG also displayed the hypolocomotor effect as compared to the control animals. Phenobarbital either alone or in combination with LTG reduced the rearing activity.
CONCLUSION: Combining LTG with valproate is advantageous because of a lack of any hypolocomotor effects, whilst the combination of LTG and carbamazepine leads to a drastic reduction in locomotor activity in animals. LTG combined with diphenylhydantoin produces a substantial decrease in the activity in mice, whereas phenobarbital alone exclusively reduces the rearing activity of the animals tested.