Levodopa reverses gait asymmetries related to anhedonia and magical ideation.

Animals and men turn preferentially away from the hemisphere with the more active dopamine (DA) system. Consistent with the idea of a right-hemispheric hyperdopaminergia in schizophrenia, a leftsided turning bias was described for unmedicated psychotic patients. We investigated the modulating role of DA and schizophrenia-like thought on whole-body turns in a controlled double-blind study. The number of veers to either side when walking blindfolded straight ahead (20 meter) was assessed in 40 healthy righthanded men (20 men received levodopa, the remaining participants placebo). Side preferences were analyzed in terms of individuals' positive (Magical Ideation, MI) and negative (Physical Anhedonia, PhysAn) schizotypal features. In the placebo group, increasing MI scores were related to increasing left-sided veering and increasing PhysAn scores were related to increasing right-sided veering. In the levodopa group, this relationship between preferred veering side and type of schizotypy was reversed. The finding in the placebo group suggests an association between MI and a relative right-hemispheric hyperdopaminergia. Unexpectedly, levodopa did not enhance this veering bias, but reversed it, suggesting that psychosis-protective mechanisms exist in the healthy positive "schizotypic" brain. Also unexpectedly, levodopa made "anhedonics" veer like "magics" after placebo, suggesting that DA agonists suppress negative schizotypal symptoms.

Effect of one month's treatment with peripherally acting catechol-O-methyltransferase inhibitor, entacapone, on pharmacokinetics and motor response to levodopa in advanced parkinsonian patients.

Twelve parkinsonian patients with levodopa-related end-of-dose fluctuations in disability were studied in an open-label trial to examine the effects of peripheral catechol-O-methyltransferase (COMT) inhibition with entacapone on pharmacokinetics and metabolism of levodopa and on clinical response to levodopa after a single dose and after 4 weeks' medication with entacapone. The clinical response was assessed with continuous monitoring using the motor part of Unified Parkinson's Disease Rating Scale. Entacapone increased statistically significantly the mean area under the plasma concentration-time curve (AUC) of levodopa by 29% after a single dose and by 21% after 4 weeks' administration, without affecting other pharmacokinetic parameters of levodopa. The AUC of 3-O-methyldopa decreased by 45% and AUC of homovanillic acid by 21% after 4 weeks' dosing with entacapone. The duration of motor response to levodopa increased significantly from 2.3 h to 3.2 h (i.e., by 39%) after a single dose and to 3.4 h (i.e., by 48%) after 4 weeks' medication with entacapone. The magnitude of clinical response remained unchanged, but peak latency of motor response was prolonged after 4 weeks' medication. The duration and magnitude of dyskinesias also increased. Peripheral COMT inhibition with entacapone increased significantly the bioavailability of levodopa and prolonged its antiparkinsonian effect after a single dose and after repeated dosing for 4 weeks. Thus entacapone seems to be a valuable adjuvant to levodopa treatment in parkinsonian patients with end-of-dose failure.