Are "on-off" effects during chronic L-dopa treatment due to faulty feedback control of the nigrostriatal dopamine pathway?

The paper reviews evidence for and against the hypothesis that the "on-off" effects observed during chronic L-dopa therapy are due to faulty feedback control of the dopaminergic nigrostriatal pathway. Such failure may be brought about by preferential desensitization of the presynaptic dopaminergic autoreceptors or by a defect in the striatonigral feedback loop. To further analyze the mechanisms underlying "on-off" effects, the development of specific dopaminergic receptor agonists, suitable for clinical investigation, might prove useful. This may be true, for example, of selective dopaminergic autoreceptor agonists, such as 3-PPP, developed by the author's research group.