title: Are "on-off" effects during chronic L-dopa treatment due to faulty feedback control of the nigrostriatal dopamine pathway?
abstract: 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.
mesh_terms: D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects*; D004298:Dopamine / Q000378:metabolism*; D005246:Feedback; D006801:Humans; D007980:Levodopa / Q000009:adverse effects* / Q000627:therapeutic use; D009434:Neural Pathways / Q000187:drug effects; D010300:Parkinson Disease / Q000188:drug therapy*; D011954:Receptors, Dopamine / Q000187:drug effects; D013378:Substantia Nigra / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects*
chemical_list: D011954:Receptors, Dopamine; D007980:Levodopa; D004298:Dopamine