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A double-blind crossover, placebo-controlled study of the adenosine A2A
antagonist theophylline in Parkinson's disease.

Kulisevsky J, Barbanoj M, Gironell A, Antonijoan R, Casas M, Pascual-Sedano B.

Movement Disorders Unit, Department of Neurology, Sant Pau Hospital,
Autonomous University of Barcelona, Spain.

Blockade of the adenosine A2A receptor potentiates the effects of levodopa in
experimental animals and may offer a novel nondopaminergic target for drug
therapy in Parkinson's disease (PD). Open-label trials suggest that the
nonspecific adenosine antagonist theophylline improves parkinsonian symptoms
and increases ON time in advanced patients with PD. In a double-blind,
crossover, placebo-controlled trial, the authors investigated the ability of
stable plasma levels of theophylline (between 10-20 microg/mL after 15 days
of treatment) to modulate the long-duration response and the short-duration
response of levodopa in 10 patients with PD. Although theophylline induced a
longer duration of the effect of levodopa in all Unified Parkinson's Disease
Rating Scale variables considered, including dyskinesias, maximal
levodopa-induced improvement and the duration of the effect of levodopa did
not differ significantly from placebo. Only the secondary variable "akinesia"
showed a statistical tendency to a more prolonged beneficial response with
theophylline during an acute levodopa test (short-duration response), and
tremor worsened with theophylline during levodopa withdrawal (long-duration
response). No differences were observed during the subacute course of study
medication added to levodopa. During this exploratory study, the effects of
theophylline were not strong enough to potentiate clearly the
antiparkinsonian action of levodopa or to increase ON time in patients with
advanced PD.

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