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

• Published in: European journal of pharmacology Vol. 369; no. 3; pp. 313 - 317
• Main Authors: VON LUBITZ, D. K. J. E, LIN, R. C.-S, BISCHOFBERGER, N, BEENHAKKER, M, BOYD, M, LIPARTOWSKA, R, JACOBSON, K. A
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier 26.03.1999
• Subjects: Adenosine - administration & dosage; Adenosine - analogs & derivatives; Adenosine - therapeutic use; Analysis of Variance; Animals; Biological and medical sciences; Brain Ischemia - drug therapy; Brain Ischemia - prevention & control; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Gerbillinae; Hippocampus - drug effects; Injections, Intraperitoneal; Medical sciences; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems; Pharmacology. Drug treatments; Purinergic P1 Receptor Agonists; Nervous system diseases; Agonist; Rodentia; A1 Adenosine receptor; Cardiovascular disease; Neuroprotective agent; Biological activity; Cerebral disorder; Vascular disease; Vertebrata; Mammalia; Ischemia; Structure activity relation; Animal; Central nervous system disease; Antiïschemic; Mechanism of action; Gerbil; Cerebrovascular disease; Brain (vertebrata)
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(99)00073-4

Although the selectivity and potency of adenosine amine congener (ADAC) at adenosine A1 receptors are similar to other highly selective agonists at this receptor type, the chemical structure of the N6 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 A1 receptor agonist-mediated neuroprotection. Most significantly, chronic treatment with low microgram doses of ADAC (25-100 microg/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 microg/kg also results in a statistically significant reduction of postischemic mortality and morbidity. These data indicate that, contrary to other adenosine A1 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 receptors appear to be involved.