Chronic administration of selective adenosine A1 receptor agonist or antagonist in cerebral ischemia

• Published in: European journal of pharmacology Vol. 256; no. 2; pp. 161 - 167
• Main Authors: VON LUBITZ, D. K. J. E, LIN, R. C.-S, MELMAN, N, XIAO-DUO JI, CARTER, M. F, JACOBSON, K. A
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier 21.04.1994
• Subjects: Adenosine - analogs & derivatives; Adenosine - therapeutic use; Animals; Biological and medical sciences; Body Temperature - drug effects; Brain Ischemia - drug therapy; Brain Ischemia - pathology; Down-Regulation - drug effects; Female; Gerbillinae; Hippocampus - drug effects; Hippocampus - metabolism; Medical sciences; Neuropharmacology; Neuroprotective agent; Pharmacology. Drug treatments; Prosencephalon - pathology; Purinergic P1 Receptor Antagonists; Receptors, Purinergic P1 - drug effects; Receptors, Purinergic P1 - metabolism; Up-Regulation - drug effects; Xanthines - therapeutic use; Nervous system diseases; Agonist; Rodentia; A1 Adenosine receptor; Cardiovascular disease; Neuroprotective agent; Cerebral disorder; Vascular disease; Vertebrata; Mammalia; Ischemia; Animal; Central nervous system disease; Antagonist; Gerbil; Cerebrovascular disease; Hippocampus; Brain (vertebrata)
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/0014-2999(94)90241-0

The effect of chronic administration of selective adenosine A1 receptor agonists and antagonists on the outcome of cerebral ischemia is entirely unknown. Therefore, we have investigated the impact of such regimens on the hippocampal adenosine A1 receptor density, and on the recovery from 10 min forebrain ischemia in gerbils. While acutely administered N6-cyclopentyladenosine (CPA) given at 0.02 mg/kg resulted only in a significant reduction of mortality, at 1 mg/kg it improved both survival and neuronal preservation in the hippocampal CA1 region. Acute treatment with 1,3-dipropyl-8-cyclopentylxanthine (CPX) significantly worsened the outcome and enhanced neuronal destruction. The effects of chronic administration of these drugs (15 days followed by 1 drug-free day) were opposite. Thus, although chronic CPA at 0.02 mg/kg did not have any effect at all, at 1 mg/kg both survival and neuronal preservation were significantly poorer than in controls, while chronic CPX resulted in a significant improvement of both measures. These results were not accompanied by adenosine A1 receptor up- or downregulation. Our study indicates that highly selective adenosine analogues may have therapeutic potential in treatment of cerebral ischemia/stroke and possibly other neurodegenerative disorders as well.