Safety and effectiveness of istradefylline in patients with Parkinson's disease: interim analysis of a post-marketing surveillance study in Japan.

BACKGROUND: Istradefylline is a first-in-class, non-dopaminergic, selective adenosine A2A receptor antagonist for the treatment of Parkinson's disease (PD) in patients experiencing the wearing-off phenomenon with levodopa (L-DOPA). The authors present an interim report from a post-marketing surveillance (PMS) evaluating the safety and effectiveness of long-term istradefylline in a real-world setting. RESEARCH DESIGN AND METHODS: Istradefylline safety was assessed by the incidence of adverse events (AE) and adverse drug reactions (ADRs). Effectiveness was assessed using the physician's assessment of off-time, off-time symptoms and motor dysfunction, unified PD rating scale (UPDRS) Part III score, and the physician's global assessment. RESULTS: This analysis evaluated 476 patients. Istradefylline was generally well tolerated, despite dyskinesia and hallucination being the most common ADRs. Reduction in off-time was observed in 38.2% of patients, off-time symptoms were improved or markedly improved in 44.7%, and motor dysfunction was improved or markedly improved in 48.5%. The mean UPDRS Part III score decreased from 33.7 to 30.3 at the end of the study. The physician's global assessment rated the drug as effective in 61.3% of patients. CONCLUSIONS: This PMS provides useful safety and effectiveness data for long-term treatment with istradefylline in a real-world setting for patients with PD exhibiting the wearing-off phenomenon with L-DOPA.

Plant volatiles regulate the activities of Ca2+ -permeable channels and promote cytoplasmic calcium transients in Arabidopsis leaf cells.

A variety of plant species emit volatile compounds in response to mechanical stresses such as herbivore attack. Although these volatile compounds promote gene expression leading to anti-herbivore responses, the underlying transduction mechanisms are largely unknown. While indirect evidence suggests that the cytoplasmic free Ca(2+) concentration ([Ca(2+)](c)) plays a crucial role in the volatile-sensing mechanisms in plants, these roles have not been directly demonstrated. In the present study, we used Arabidopsis leaves expressing apoaequorin, a Ca(2+)-sensitive luminescent protein, in combination with a luminometer, to monitor [Ca(2+)](c) transients that occur in response to a variety of volatile compounds and to characterized the pharmacological properties of the increase in [Ca(2+)](c). When leaves were exposed to volatiles, [Ca(2+)](c) was transiently raised. The [Ca(2+)](c) increases induced by acyclic compounds were disrupted by Ruthenium Red, a potential plasma-membrane and endo-membrane Ca(2+)-permeable channel inhibitor, but not by 1,2-bis(2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid (BAPTA), an extracellular Ca(2+)-chelator, suggesting that acyclic compounds promote Ca(2+)-release from intracellular stores. On the other hand, the electrophilic compound (E)-2-hexenal promoted Ca(2+)-influx via ROS production by natural oxidation at the aquarius phase. In a gpa1-2 mutant lacking a canonical Galpha subunit, the [Ca(2+)](c) transients induced by all tested volatiles were not attenuated, suggesting that G-protein coupled receptors are not involved in the volatile-induced [Ca(2+)](c) transients in Arabidopsis leaves.