These findings suggest that amantadine given as adjuvant to levodopa can markedly improve motor response complications and support the view that hyperfunction of NMDA receptors contributes to the pathogenesis of levodopa-associated motor complications.

Tourette's Syndrome (TS) is a poorly understood neurological disorder characterized by multiple motor and phonic tics and associated behavioral disturbances. While TS is clearly a disorder of motor function, the nature of the tics and the associated cognitive and behavioral features suggest that the pathogenesis extends beyond the motor domain. The motivational tension that commonly precedes motor and vocal tics and the sense of relief that follows their expression, as well as the irritability, impulsivity, depression or self-injurious behavior that may characterize more complex cases, all tend to suggest that brain regions associated with motivation or affect may also be involved. The generation of symptoms in TS might in fact reflect an abnormality of brain systems that effect neural transmission from the limbic

Wearing-off phenomenon that complicates levodopa therapy of Parkinson's disease has been attributed to a reduction in striatal dopamine storage due to the progressive degeneration of presynaptic dopaminergic terminals. To determine whether postsynaptic mechanisms also contribute to these response fluctuations, the duration of the antiparkinsonian response in parkinsonian patients grouped by disease severity was compared following discontinuation of a steady-state optimal-dose infusion of apomorphine. Although the plasma half-life of this dopamine receptor agonist remained constant, its mean efficacy half-time declined from 66 minutes in early, levodopa-naive patients to 33 minutes in advanced, complicated parkinsonians (p < 0.005). Since the motor effects of apomorphine do not depend on the presence of dopaminergic terminals, changes at the postsynaptic level undoubtedly contribute to the diminished response duration. The only slightly greater attenuation of levodopa's motor effects observed previously under similar conditions suggests these postjunctional alterations, possibly involving relatively plastic striatal dopaminoceptive systems, account for most of the shortening in the duration of levodopa action that underlie wearing-off fluctuations.

No abstract