Antiglutamatergic acting substances are considered to be useful tools for the treatment of hypokinesia in animal models for Parkinson's disease (PD). Moreover, most known antiglutamatergic compounds act postsynaptically and are either toxic or weak with regard to their clinical potency. The antiepileptic drug "Lamotrigine (LTG)" inhibits presynaptic glutamate release and may therefore provide a novel approach for PD therapy. Encouraging results from a pilot project led us to establish a placebo controlled trial including 20 patients with PD. The substance was generally well tolerated. There was a significant difference in the investigator's overall assessment of efficacy (6/10 vs. 2/10 improvement; p < 0.05) and a tendency for LTG to exhibit a beneficial effect in some registration parameters, but no significant differences in motor response were found between the two groups. We failed to confirm that LTG mediates a strong antiparkinsonian effect in this small study, but to clearly demonstrate slight or moderate beneficial effects larger groups are required.