REDUCTION OF POSTISCHEMIC BRAIN-DAMAGE AND MEMORY DEFICITS FOLLOWING TREATMENT WITH THE SELECTIVE ADENOSINE A(1) RECEPTOR A AGONIST

Agonists of adenosine A(1) receptors have been frequently proposed as candidate, for clinical development in treatment of cerebral ischemia and stroke, Numerous experimental studies have shown that pre- and pos tischemic administration of these drugs results in a very significant reduction of postischemic brain damage. However, only a few studies de termined the impact of cerebral ischemia and drug treatment on postisc hemic recovery of spatial memory. Thr present paper demonstrates that preischemic i.p. administration of adenosine amine congener(ADAC) at 1 00 mu g/kg in gerbils results in a significant (P < 0.05) reduction of postischemic mortality and hippocampal, cortical and striatal morbidi ty. Postischemic Morris' water maze tests show that preischemic treatm ent with ADAC also leads to a very significant (P < 0.001) reduction o f postischemic spatial memory loss, Our results indicate feasibility o f further consideration of adenosine A(1) receptor agonists as a clini cally applicable acute treatment of brain ischemia. Recent development of neuroprotective adenosine A(1) receptor agonists that are free of cardiovascular side effects supports such development.