Background: Gait disorders are common in Parkinson’s disease patients who respond poorly to dopaminergic treatment. Blockade of adenosine A2A receptors is expected to improve gait disorders. Istradefylline is a first-in-class selective adenosine A2A receptor antagonist with benefits for motor complications associated with Parkinson’s disease.
Research design and methods: This multicenter, open-label, single-group, prospective interventional study evaluated changes in total gait-related scores of the Part II/III Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) and Freezing of Gait Questionnaire (FOG-Q) in 31 Parkinson’s disease patients treated with istradefylline. Gait analysis by portable gait rhythmogram was performed.
Results: MDS-UPDRS Part III gait-related total scores significantly decreased at Weeks 4–12 from baseline with significant improvements in gait, freezing of gait, and postural stability. Significant decreases in MDS-UPDRS Part II total scores and individual item scores at Week 12 indicated improved daily living activities. At Week 12, there were significant improvements in FOG-Q, new FOG-Q, and overall movement per 48 h measured by portable gait rhythmogram. Adverse events occurred in 7/31 patients.
Conclusions: Istradefylline improved gait disorders in Parkinson’s disease patients complicated with freezing of gait, improving their quality of life. No unexpected adverse drug reactions were identified.
In isolated rat lungs subjected to fat emulsion damage, a model simulating adult respiratory distress syndrome, we have previously reported that adenosine (ADO) reduces pulmonary vascular resistance (PVR) and the fluid filtration rate (FFR). In the present study the aim was to examine morphologically this effect of ADO. Two groups of isolated rat lungs were subjected to the injury. Marked and significant differences were found between the groups; in lungs not given ADO, FFR and airway pressure were higher and, as evaluated by electron microscopy, the endothelial lining was thin and partly disrupted. The epithelial cells of the alveolar walls were also partly disrupted and the alveolar septa were split enclosing interstitial edema. In lungs receiving ADO from the onset of exposure to fat emulsion, FFR was lower and ultrastructure did not differ from non–injured non–treated controls perfused for the same length of time. 相似文献
In order to analyze the epileptogenic mechanisms of caffaine and related xanthines, putative effects of these drugs were studied on adenosine receptors of CA3 neurons in hippocampal slices. Epileptogenic concentrations of different xanthine derivatives strongly correlated with their affinities for the inhibitory A1 adenosine receptor subtype. The A1 receptor agonists adenosine and R-PIA reversibly depressed xanthine-induced epileptic activity without effects on the resting membrane potential or on spontaneously occuring action potentials. These findings suggest that the epileptogenic potency of xanthines is primarily due to the blockade of the A1 receptors through an abnormal rise of intracellular cAMP and to the excessive transmembrane calcium fluxes underlying paroxysmal depolarization shifts. 相似文献