Protection against ischemic damage by adenosine amine congener, a potent and selective adenosine A(1) 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 comple tely different. We now demonstrate that the characteristics of the therapeu tic profile of ADAC are distinct from those observed during our previous st udies of adenosine A(1) receptor agonist-mediated neuroprotection. Most sig nificantly, 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 statis tical significance of the protective effect is lost. Acute preischemic admi nistration of the drug at 75-200 mu g/kg also results in a statistically si gnificant reduction of postischemic mortality and morbidity. These data ind icate that, contrary to other adenosine A(1) receptor agonists whose chroni c administration enhances postocclusive brain damage, ADAC may be a promisi ng agent in treatment of both acute (e.g., cerebral ischemia) and chronic ( seizures) disorders of the central nervous system in which adenosine A(1) r eceptors appear to be involved. (C) 1999 Elsevier Science B.V. All rights r eserved.