PREFACE Most diseases resulting from brain dysfunction are very tragic not only for the patients themselves but also for their families because these diseases deprive them of both the quality of human life and often compassion. The brain is one of the last frontiers in modern biology, with many unknown mechanisms. Thereby, the areas of neurology and psychiatry are the most challenging for scientists those whose goal is to open the gates to new cures for diseases involving the brain. Adenosine is a purine ribonucleoside and is ubiquitously distributed throughout the mammalian body. Since the 1920s, adenosine and purine receptors have been studied extensively in biomedical research. Approximately an 80-year journey of research already traveled by great ancestors stands before us. Since the beginning of research, there have been significant outcomes ensuring that the adenosine and purine families contribute to the mammalian cardiovascular system, including vasodilation and heart function. It should be noted that the progression of receptor science has always been supported by molecular biology for receptor classification and promoted via the appearance of pharmacological tools like selective agonists and antagonists to identify receptor function. These tools also sometimes become known in the development of medicines as new therapeutics themselves. Adenosine receptor science is, of course, not an exception. In the early 1970s, it was proposed that adenosine was an important neuromodulator in both the peripheral and central nervous systems. This was evidenced by studies using methylxanthines, such as caffeine and theophylline, as antagonists at adenosine receptors. Furthermore, in the beginning of the 1990s, we saw an explosion of adenosine receptor science because molecular biology and pharmacology identified the four adenosine receptor subtypes: the A1, A2A, A2B, and A3 receptors. At the same time, caffeine, a nonselective adenosine antagonist, was still widely employed in many studies, including human epidemiology, as a kind of unique contribution for the field, until selective receptor agents were invented (for example, a cup of coffee containing caffeine made science close to many people’s mind). Recently, receptor selective agents were created to assist and accelerate the entire research effort, which often brought to light particular physiological functions of adenosine as a neuromodulator/neurotransmitter. Some of xv

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the adenosine agents also became new candidates as medicines for the treatment of brain dysfunction. Due to the nature of adenosine, which is a ubiquitous modulator of cellular activity, it is not surprising that there is a growing body of interest for adenosine and its receptors and their role as new and broad targets for research of brain function and dysfunction. I invited distinguished scientists, who are working to further adenosine receptor science by seeking new therapies for a number of CNS diseases as well as adenosine function in the brain, to contribute to this volume. These scientists participated enthusiastically by sharing their new insights, knowledge, therapeutic strategies, views, and future applications for adenosine receptor science from multiple disease and brain functional perspectives, such as Parkinson’s disease, Huntington’s disease, epilepsy, cognitive function, cerebral ischemia, sleep, depression, anxiety, and schizophrenia. In the early 1990s, when I started to work in the research area of adenosine receptor function in the brain, I did not have any idea like I do today that there could be so many aspects and practical ideas for new therapies involving adenosine receptors, as described in this volume. Now, I am very confident knowing that tomorrow will be more fantastic and will produce practical cures for neurological and psychiatric diseases from the continued research and progression of adenosine receptor science. Finally, I would like to acknowledge the tremendous efforts and huge insights made into adenosine receptor science by my colleagues and contributors for this volume. AKIHISA MORI Cherry blossom season in Tokyo, 2014