A review with 51 refs. Adenosine regulates several physiol. functions through specific cell membrane receptors. On the basis of pharmacol. studies and mol. cloning, four distinct adenosine receptors have been identified and classified as A1, A2A, A2B and A3. These adenosine receptors are members of the G-protein coupled receptor family, but while A2A and A2B receptors stimulate adenylyl cyclase with a consequent increase of cAMP levels, A1 and A3 receptor subtypes produce the opposite effect. Intense efforts made over the last 20 yr have led to the synthesis of a variety of selective adenosine agonists. In general, all of the compds. thus far identified are related to the adenosine structure. The A1 receptors are usually found on the working cells of tissues (e.g., neurons and cardiomyocytes) and mediate decreases in oxygen demand; for these reasons A1 agonists could be useful for the treatment of, for example, renal failure, arrhythmias, diabetes Type II, myocardial ischemia and neurodegenerative disorders. The A3 receptor is not yet well known. This receptor subtype seems involved in inflammatory and neurodegenerative diseases, asthma and cardiac ischemia but some paradoxical effects have been obsd. On the basis, the recent developments on structure-activity relationships at A1 and A3 receptors and their possible use as therapeutic agents are reviewed, with particular emphasis on recent patent literature.
A(1) and A(3) adenosine receptor agonists: an overview
BARALDI, Pier Giovanni;CACCIARI, Barbara;ROMAGNOLI, Romeo;
1999
Abstract
A review with 51 refs. Adenosine regulates several physiol. functions through specific cell membrane receptors. On the basis of pharmacol. studies and mol. cloning, four distinct adenosine receptors have been identified and classified as A1, A2A, A2B and A3. These adenosine receptors are members of the G-protein coupled receptor family, but while A2A and A2B receptors stimulate adenylyl cyclase with a consequent increase of cAMP levels, A1 and A3 receptor subtypes produce the opposite effect. Intense efforts made over the last 20 yr have led to the synthesis of a variety of selective adenosine agonists. In general, all of the compds. thus far identified are related to the adenosine structure. The A1 receptors are usually found on the working cells of tissues (e.g., neurons and cardiomyocytes) and mediate decreases in oxygen demand; for these reasons A1 agonists could be useful for the treatment of, for example, renal failure, arrhythmias, diabetes Type II, myocardial ischemia and neurodegenerative disorders. The A3 receptor is not yet well known. This receptor subtype seems involved in inflammatory and neurodegenerative diseases, asthma and cardiac ischemia but some paradoxical effects have been obsd. On the basis, the recent developments on structure-activity relationships at A1 and A3 receptors and their possible use as therapeutic agents are reviewed, with particular emphasis on recent patent literature.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
