Apomorphine responses in Parkinson's disease and the pathogenesis of motor complications.
We studied the contribution of basal ganglia circuitry downstream from the nigrostriatal dopaminergic system to the pathogenesis of levodopa associated motor complications by means of an apomorphine dose-response paradigm in 28 parkinsonian patients grouped according to their clinical response to levodopa therapy. With progression from the dopa-naive to the severely fluctuating dyskinetic state, apomorphine response duration shortened, the dose-response slope steepened, and the therapeutic window narrowed. Because apomorphine acts independently of the integrity of presynaptic dopaminergic neurons, our results suggest that postsynaptic alterations account mainly for the appearance of response complications. The present findings support the possibility, raised by animal model studies, that motor response complications arise as a consequence of altered signal transduction mechanisms in striatal medium-sized neurons.
Verhagen Metman
L
L
Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD.
Locatelli
E R
ER
Bravi
D
D
Mouradian
M M
MM
Chase
T N
TN
D001058:Apomorphine / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009069:Movement Disorders / Q000188:drug therapy; D010300:Parkinson Disease / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D010919:Placebos; D011954:Receptors, Dopamine; D017661:Receptors, Presynaptic
D010919:Placebos; D011954:Receptors, Dopamine; D017661:Receptors, Presynaptic; D001058:Apomorphine