Pathophysiology of L-dopa-induced abnormal involuntary movements.
Among the various deficiencies in neurotransmitters and neuropeptides in the brains of patients with Parkinson's disease, the loss of dopamine (DA) is implicated in a major way in the occurrence of L-dopa-induced abnormal involuntary movements (AIMs). Whatever the clinical pattern, they are triggered by drugs which stimulate DA transmission and can be modified by DA agonists and antagonists. They occur when DOPA plasma concentrations, and thus central DA receptor stimulation, reach a critical level. They are observed in patients with severely damaged central DA neurons, but involvement of other neurotransmitter-containing cells cannot be excluded. L-Dopa-induced AIMs have clinical and somatotopic characteristics, which vary from patient to patient. One might speculate that variable damage to DA neurons, associated or not with other neurotransmitter-containing cells in the affected brain structures, causes these differences in AIM patterns. By analogy with behavioral experiments in animals, the hypersensitivity of DA receptors observed in the basal ganglia of parkinsonian patients post mortem might reasonably be considered to mediate L-dopa-induced AIMs. However, the role of various subtypes of DA receptors or of changes in DA metabolism in the cell bodies and dendrites (substantia nigra) or nerve terminals (striatolimbic areas) must also be considered. In brief, the features, topography, and timing of L-dopa-induced AIMs are dependent upon alterations of the functional expression of striatal DA output, which is not yet well understood.
Agid
Y
Y
Bonnet
A M
AM
Ruberg
M
M
Javoy-Agid
F
F
D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D003342:Corpus Striatum / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism; D004409:Dyskinesia, Drug-Induced / Q000503:physiopathology*; D006801:Humans; D007980:Levodopa / Q000009:adverse effects* / Q000378:metabolism / Q000627:therapeutic use; D009434:Neural Pathways / Q000187:drug effects; D010300:Parkinson Disease / Q000188:drug therapy*; D011954:Receptors, Dopamine / Q000187:drug effects; D013134:Spiperone / Q000378:metabolism; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology; D013378:Substantia Nigra / Q000187:drug effects; D013569:Synapses / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects
D011954:Receptors, Dopamine; D007980:Levodopa; D013134:Spiperone; D004298:Dopamine