On-off response. Clinical and biochemical correlations during oral and intravenous levodopa administration in parkinsonian patients.

Seven parkinsonian patients who had severe on-off effects during chronic treatment with levodopa were studied. Marked swings in plasma dopa levels as well as in motor function followed each oral dose of levodopa. A constant intravenous infusion of levodopa resulted in stable plasma dopa concentrations and virtual disappearance of motor fluctuations. Notwithstanding steady plasma dopa levels, an abrupt decline in the antiparkinsonian response to levodopa attended postural tilting or cold pressore stimulation. Although these maneuvers were accompanied by a significant rise in plasma norepinephrine, the intravenous infusion of this catecholamine failed to influence the effect of levodopa on parkinsonian signs. The results suggest that central noradrenergic mechanisms as well as alterations in circulating dopa may contribute to the on-off response to levodopa.