title: Doridosine derivatives: binding at adenosine receptors and in vivo effects.
abstract: Doridosine, an adenosine analogue, causes, in vivo, hypotension, reduction of heart rates, muscle relaxation and anti-inflammatory effects through adenosine A1 and A2 receptors. A series of doridosine derivatives was synthesized in a search for compounds with more selective adenosine A1 receptor activity. These derivatives were characterized for binding to the respective adenosine receptors and for their cardiovascular effects. We used competition binding studies with highly selective radioligands: [3H]cyclohexyladenosine for adenosine A1 and [3H]CGS 21680 for adenosine A2 binding assays. The results for eight doridosine derivatives revealed that 1-cyclopropylisoguanosine (BN-063) and 1-allylisoguanosine (AZ-108-1) were more selective for the adenosine A1 receptor. In vivo, both BN-063 and AZ-108-1 caused significant bradycardia but no obvious effect on blood pressure. The bradycardia was almost completely blocked by 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, a specific adenosine A1 receptor antagonist).
authors.affiliation: Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan, ROC.
authors.forename: P L
authors.initials: PL
authors.lastname: Tao
authors.forename: M H
authors.initials: MH
authors.lastname: Yen
authors.forename: W S
authors.initials: WS
authors.lastname: Shyu
authors.forename: J W
authors.initials: JW
authors.lastname: Chern
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics* / Q000494:pharmacology*; D001667:Binding, Competitive / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002540:Cerebral Cortex / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D005260:Female; D006151:Guanosine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D018047:Receptors, Purinergic P1 / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000959:Antihypertensive Agents; D018047:Receptors, Purinergic P1; D006151:Guanosine; C022591:doridosine