Book: The Adenosinergic System: A Non-Dopaminergic Target in Parkinson’s Disease

[Farooqji]

Adenosine A2A receptor antagonists have shown great promise in the treatment of Parkinson's Disease and alleviation of symptoms. This book addresses various aspects of this class of drugs from their chemical development to their clinical use.

books.google.com.pk/books/a...

[Farooqji]

Preface

Parkinson’s disease is the second most common neurodegenerative disorder after Alzheimer’s disease, and affects more than 5 million people worldwide. Today, the clinical management of Parkinson’s disease chiefly relies on the use of the so called “dopamine replacement therapy” in order to re-establish the function of the dopaminergic system, which is affected by the neurodegeneration underlying the disease. While this approach effectively counteracts the motor deficits featuring Parkinson’s disease, the chronic use of dopamine replacement therapy eventually leads to the emergence of motor complications (e.g., dyskinesia and motor fluctuations) that greatly limit its therapeutic potential. Moreover, dopamine replacement therapy has no apparent beneficial effects on the progression of dopaminergic degeneration featuring Parkinson’s disease. Based on these considerations, there is a need for the development of alternative therapies that could help to overcome these limitations. In these years, drugs acting as antagonists of the adenosine A2A receptors have

emerged as new promising candidates for the therapy of Parkinson’s disease. When evaluated in experimental animal models of the disease, these drugs counteract motor deficits and amplify the beneficial effects of dopaminergic drugs without worsening their dyskinetic effect. Moreover, experimental evidence also indicates that adenosine A2A receptor antagonists might slow down or arrest the dopaminergic degeneration that underlies Parkinson’s disease. Building on this evidence, the research in this field has recently made significant progress, leading to the approval of the first A2A receptor antagonist for clinical use as adjunct to L-DOPA (istradefylline, marketed under the name of NOURIAST®), and the ongoing clinical evaluation of other promising drugs (e.g., tozadenant). This book covers basic biological aspects of the adenosine system relevant to Parkinson’s disease, and also discusses recent experimental findings at both the preclinical and clinical level. Attention is dedicated to the localization and function of adenosine A2A receptors, to their interaction with dopaminergic and nondopaminergic receptors in the brain, and to the development of novel molecules that may target A2A receptors. The critical role of the adenosine system in the regulation of neurotrophic factors, neuroinflammation, and neurotoxicity is also covered, and the relevance of these phenomena to the etiology of Parkinson’s disease discussed. Moreover, the book thoroughly describes the effects of adenosine A2A receptor

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