A TRIAL OF DEXTROMETHORPHAN IN PARKINSONIAN-PATIENTS WITH MOTOR RESPONSE COMPLICATIONS

The effects of the NMDA antagonist dextromethorphan (DM) on levodopa-a ssociated dyskinesias and motor fluctuations were studied in patients with advanced Parkinson's disease. During initial open-label dose esca lation, 6 of 18 patients reported a beneficial effect at their individ ually determined optimal DM dose (range, 60-120 mg/day). The 12 remain ing patients either experienced reversible side effects, particularly mild drowsiness, or decreased levodopa efficacy, and were therefore ex cluded from the study. The six responders entered the double-blind. pl acebo-controlled, crossover study with two 2-week arms separated by 1 week wash-out. On the last day of each arm, motor ratings were perform ed every 20 minutes for g consecutive hours. In addition, motor compli cations and Activities of Daily Living (ADL) were assessed using the U nified Parkinson's Disease Rating Scale (UPDRS) and patient diaries. W ith Dh?, dyskinesias improved by 25% according to physician's ratings and by 40% according to UPDRS interviews, without compromising the ant i-Parkinson effect of Ievodopa. Motor fluctuations and ADL scores also improved significantly. Although the narrow therapeutic index of DM l imits its clinical usefulness, these findings support the view that dr ugs acting to inhibit glutamatergic transmission at tile NMDA receptor can ameliorate levodopa-associated motor complications.