Adenosine as a modulator of brain activity.
The endogenous neuromodulator adenosine controls and integrates a wide range of brain functions. Consequently, dysfunction of the adenosine system is involved in pathologies ranging from epilepsy to neurodegenerative disorders and psychiatric conditions. The adenosine system has therefore been recognized as a prime target for the development of new therapeutics for neurological diseases. This review covers the upstream and downstream targets of adenosinergic neurotransmission and provides the neurochemical rationale for the development of adenosine receptor modulating drugs (downstream) and inhibitors of adenosine kinase, the key upstream regulator of ambient levels of adenosine. Due to the unique role of adenosine to integrate and fine-tune glutamatergic and dopaminergic neurotransmission, adenosine-regulating agents have the potential to modify a wide range of downstream effects. Thus, adenosine-based therapies are rapidly evolving in preclinical and clinical studies.
Boison
Detlev
D
R.S. Dow Neurobiology Laboratories, Portland, Oregon 97232, USA. dboison@downeurobiology.org
D000241:Adenosine / Q000378:metabolism*; D000248:Adenosine Kinase / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002986:Clinical Trials as Topic; D016503:Drug Delivery Systems; D004353:Drug Evaluation, Preclinical; D006801:Humans; D009422:Nervous System Diseases / Q000188:drug therapy / Q000503:physiopathology; D043682:Receptor, Adenosine A1 / Q000187:drug effects / Q000378:metabolism; D043705:Receptor, Adenosine A2A / Q000187:drug effects / Q000378:metabolism
D043682:Receptor, Adenosine A1; D043705:Receptor, Adenosine A2A; D000248:Adenosine Kinase; D000241:Adenosine