Protection against ischemic damage by adenosine amine congener, a potent and selective adenosine A1 receptor agonist

Although the selectivity and potency of adenosine amine congener (ADAC) at adenosine A(1) receptors are similar to other highly selective agonists at this receptor type, the chemical structure of the N-6 substituent is completely different. We now demonstrate that the characteristics of the therapeutic profile of ADAC are distinct from those observed during our previous studies of adenosine A(1) receptor agonist-mediated neuroprotection. Most significantly, chronic treatment with low microgram doses of ADAC (25-100 mu g/kg) protects against both mortality and neuronal damage induced by 10 min bilateral carotid occlusion in gerbils. At higher chronic doses, the statistical significance of the protective effect is lost. Acute preischemic administration of the drug at 75-200 mu g/kg also results in a statistically significant reduction of postischemic mortality and morbidity. These data indicate that, contrary to other adenosine A(1) receptor agonists whose chronic administration enhances postocclusive brain damage, ADAC may be a promising agent in treatment of both acute (e.g., cerebral ischemia) and chronic (seizures) disorders of the central nervous system in which adenosine A(1) receptors appear to be involved. (C) 1999 Elsevier Science B.V. All rights reserved.