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Adenosine A2A Receptor Antagonists in Parkinson’s Disease: Progress in Clinical Trials from the Newly Approved Istradefylline to Drugs in Early Development and Those Already Discontinued
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Adenosine A2A Receptor Antagonists in Parkinson’s Disease: Progress in Clinical Trials from the Newly Approved Istradefylline to Drugs in Early Development and Those Already Discontinued
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Journal Article
Adenosine A2A Receptor Antagonists in Parkinson’s Disease: Progress in Clinical Trials from the Newly Approved Istradefylline to Drugs in Early Development and Those Already Discontinued
2014
Overview
Neurotransmitters other than dopamine, such as norepinephrine, 5-hydroxytryptamine, glutamate, adenosine and acetylcholine, are involved in Parkinson’s disease (PD) and contribute to its symptomatology. Thus, the progress of non-dopaminergic therapies for PD has attracted much interest in recent years. Among new classes of drugs, adenosine A
2A
antagonists have emerged as promising candidates. The development of new highly selective adenosine A
2A
receptor antagonists, and their encouraging anti-parkinsonian responses in animal models of PD, has provided a rationale for clinical trials to evaluate the therapeutic potential and the safety of these agents in patients with PD. To date, the clinical research regarding A
2A
antagonists and their potential utilization in PD therapy continues to evolve between drugs just or previously discontinued (preladenant and vipadenant), new derivatives in development (tozadenant, PBF-509, ST1535, ST4206 and V81444) and the relatively old drug istradefylline, which has finally been licensed as an anti-parkinsonian drug in Japan. All these compounds have been shown to have a good safety profile and be well tolerated. Moreover, results from phase II and III trials also demonstrate that A
2A
antagonists are effective in reducing
off-time
, without worsening troublesome dyskinesia, and in increasing
on-time
with a mild increase of non-troublesome dyskinesia, in patients at an advanced stage of PD treated with
l
-DOPA. In addition, early findings suggest that A
2A
antagonists might also be efficacious as monotherapy in patients at an early stage of PD. This review summarizes pharmacological and clinical data available on istradefylline, tozadenant, PBF-509, ST1535, ST4206, V81444, preladenant and vipadenant.
Publisher
Springer International Publishing
Subject
Adenosine A2 Receptor Antagonists - adverse effects
/ Adenosine A2 Receptor Antagonists - chemistry
/ Adenosine A2 Receptor Antagonists - pharmacology
/ Animals
/ Antiparkinson Agents - adverse effects
/ Antiparkinson Agents - chemistry
/ Antiparkinson Agents - pharmacology
/ Humans
/ Medicine
/ Parkinson Disease - drug therapy
