title: Protection against ischemic damage by adenosine amine congener, a potent and selective adenosine A1 receptor agonist.
abstract: 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.
authors.affiliation: Emergency Medicine Research Laboratories, Section of Emergency Medicine, Michigan University, Ann Arbor 48109-0014, USA. ramillies@worldnet.att.net
authors.forename: D K
authors.initials: DK
authors.lastname: Von Lubitz
authors.forename: R C
authors.initials: RC
authors.lastname: Lin
authors.forename: N
authors.initials: N
authors.lastname: Bischofberger
authors.forename: M
authors.initials: M
authors.lastname: Beenhakker
authors.forename: M
authors.initials: M
authors.lastname: Boyd
authors.forename: R
authors.initials: R
authors.lastname: Lipartowska
authors.forename: K A
authors.initials: KA
authors.lastname: Jacobson
mesh_terms: D000241:Adenosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000704:Analysis of Variance; D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005849:Gerbillinae; D006624:Hippocampus / Q000187:drug effects; D007274:Injections, Intraperitoneal; D058906:Purinergic P1 Receptor Agonists
chemical_list: D058906:Purinergic P1 Receptor Agonists; C106045:adenosine amine congener; D000241:Adenosine