Pharmacological and PET studies in patient’s with Parkinson’s disease and a short duration-motor response: implications in the pathophysiology of motor complications

Summary.

Patients with Parkinson’s disease (PD) and levodopa-induced motor complications experience a short-duration response (SDR) to levodopa which can be considered the basis of motor fluctuations. The SDR is characterized by reduced response duration, increased magnitude of the response and reduced latency to the peak effect. A short latency and a high magnitude are the most salient pharmacological features of the SDR. Its pathophysiology is not totally understood. The pharmacological characteristics of the motor response to apomorphine and their relationship with 6-[¹⁸F]fluoro-L-dopa (FDOPA) and [¹¹C]raclopride (RACLO) uptake were studied in 9 patients with PD. Latency to peak effect was positively correlated with putaminal FDOPA uptake (p<0.05) and negatively correlated with RACLO uptake (P<0.05). A trend towards significance (p:0.06) between magnitude of the response and FDOPA uptake was found which were negatively correlated. Levodopa-induced dyskinesias were negatively correlated with FDOPA uptake (p<0.05) and a trend towards significance (positive correlation) with RACLO uptake was observed (p:0.07). These results suggest that both pre and postsynaptic mechanisms are involved in the origin of the SDR.