A double-blind crossover, placebo-controlled study of the adenosine A2A antagonist theophylline in Parkinson's disease.
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.
Kulisevsky
Jaime
J
Movement Disorders Unit, Department of Neurology, Sant Pau Hospital, Autonomous University of Barcelona, Spain.
Barbanoj
Manel
M
Gironell
Alexandre
A
Antonijoan
Rosa
R
Casas
Miquel
M
Pascual-Sedano
Berta
B
D000203:Activities of Daily Living; D000368:Aged; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002230:Carbidopa / Q000008:administration & dosage / Q000627:therapeutic use; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D020820:Dyskinesias / Q000188:drug therapy; D005260:Female; D006801:Humans; D007980:Levodopa / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010300:Parkinson Disease / Q000188:drug therapy*; D058915:Purinergic P1 Receptor Antagonists; D043705:Receptor, Adenosine A2A; D013806:Theophylline / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors
D000978:Antiparkinson Agents; D003692:Delayed-Action Preparations; D058915:Purinergic P1 Receptor Antagonists; D043705:Receptor, Adenosine A2A; D007980:Levodopa; D013806:Theophylline; D002230:Carbidopa