MOTOR FLUCTUATIONS IN LEVODOPA TREATMENT - CLINICAL-PHARMACOLOGY

Fluctuations in motor performance and dyskinesias are a common problem in the long-term management of Parkinson's disease, The pharmacokinet ics and the pharmacodynamics of levodopa, loss of presynaptic dopamine terminals, alterations in postsynaptic dopamine receptor sensitivity, or changes in the modulatory influences of nondopaminergic transmitte r system could play a pathogenic role. The short half-life of levodopa and its absorption and transport are important factors. The pharmacod ynamic response to levodopa changes during long-term therapy. An absol ute threshold in plasma levodopa level, below which the patients are o ff, appears. The patients show a therapeutic window for levodopa which becomes narrower with time. This therapeutic window can be widened by giving continuous infusion of dopaminergic drugs. Motor fluctuations can be ameliorated by a more physiological continuous stimulation of t he receptor site and by avoiding repeated shifting in levodopa levels. Long-term complications are attenuated by an early combination of lev odopa with dopamine agonist.