Pulsatile stimulation of dopamine receptors and levodopa-induced motor complications in Parkinson's disease - Implications for the early use of COMT inhibitors

Increasing laboratory and clinical evidence indicates that pulsatile stimul ation of dopamine receptors contributes to the development of levodopa-rela ted motor complications in PD. In keeping with this concept, clinical trial s have demonstrated that initiating therapy with a long-acting dopamine ago nist reduces the risk of inducing motor complications in comparison to levo dopa. However, the introduction of levodopa is associated with the developm ent of motor complications even in the presence of a long-acting dopamine a gonist in both PD patients or MPTP treated monkeys. Administration of levod opa with a catechol-O-methyl transferase (COMT) inhibitor increases its pla sma half-life, smoothes out peaks and troughs, and delivers levodopa to the brain in a more continuous fashion. We hypothesize that the risk of develo ping motor complications in PD patients when levodopa is introduced can be reduced if the levodopa is coupled with a COMT inhibitor so as to provide m ore continuous dopaminergic stimulation of dopamine receptors. A proposed a lgorithm for the treatment of the early PD patient is to initiate therapy w ith a dopamine agonist, and supplement with levodopa coupled with a COMT in hibitor when the dopamine agonist cannot provide satisfactory clinical bene fits. NEUROLOGY 2000;55(Suppl 4):S72-S77.