title: Using caffeine and other adenosine receptor antagonists and agonists as therapeutic tools against neurodegenerative diseases: a review.
abstract: Caffeine is the most consumed pychostimulant in the world, and it is known to affect basic and fundamental human processes such as sleep, arousal, cognition and learning and memory. It works as a nonselective blocker of adenosine receptors (A1, A2a, A2b and A3) and has been related to the regulation of heart rate, the contraction/relaxation of cardiac and smooth muscles, and the neural signaling in the central nervous system (CNS). Since the late 1990s, studies using adenosine receptor antagonists, such as Caffeine, to block the A1 and A2a adenosine receptor subtypes have shown to reduce the physical, cellular and molecular damages caused by a spinal cord injury (SCI) or a stroke (cerebral infarction) and by other neurodegenerative diseases such as Parkinson's and Alzheimer's diseases. Interestingly, other studies using adenosine receptor agonists have also shown to provide a neuroprotective effect on various models of neurodegenerative diseases through the reduction of excitatory neurotransmitter release, apoptosis and inflammatory responses, among others. The seemingly paradoxical use of both adenosine receptor agonists and antagonists as neuroprotective agents has been attributed to differences in dosage levels, drug delivery method, extracellular concentration of excitatory neurotransmitters and stage of disease progression. We discuss and compare recent findings using both antagonists and agonists of adenosine receptors in animal models and patients that have suffered spinal cord injuries, brain strokes, and Parkinson's and Alzheimer's diseases. Additionally, we propose alternative interpretations on the seemingly paradoxical use of these drugs as potential pharmacological tools to treat these various types of neurodegenerative diseases.
authors: Department of Anatomy and Neurobiology and Institute of Neurobiology, University of Puerto Rico, Medical Sciences Campus, San Juan 00936, Puerto Rico.
authors: Marla
authors: M
authors: Rivera-Oliver
authors: Department of Anatomy and Neurobiology and Institute of Neurobiology, University of Puerto Rico, Medical Sciences Campus, San Juan 00936, Puerto Rico. Electronic address: manuel.diaz6@upr.edu.
authors: Manuel
authors: M
authors: Díaz-Ríos
mesh_terms: D000818:Animals; D002110:Caffeine / Q000627:therapeutic use*; D006801:Humans; D008954:Models, Biological; D019636:Neurodegenerative Diseases / Q000188:drug therapy*; D018696:Neuroprotective Agents / Q000627:therapeutic use; D058906:Purinergic P1 Receptor Agonists / Q000627:therapeutic use*; D058915:Purinergic P1 Receptor Antagonists / Q000627:therapeutic use*
chemical_list: D018696:Neuroprotective Agents; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D002110:Caffeine
keywords: Adenosine receptors; Alzheimer's disease; Caffeine; Parkinson's disease; Spinal cord injury; Stroke