Doridosine derivatives: binding at adenosine receptors and in vivo effects

European Journal of Pharmacology
P L TaoJ W Chern

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).

References

Feb 7, 1992·Journal of Medicinal Chemistry·K A JacobsonM Williams
Oct 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·S CotecchiaB K Kobilka
Sep 1, 1980·Analytical Biochemistry·P J Munson, D Rodbard
Mar 1, 1982·Journal of Medicinal Chemistry·J W Daly
Aug 1, 1981·Journal of Medicinal Chemistry·R T BartlettJ F Marwood

Citations

Jan 26, 2010·Marine Drugs·Marina Gordaliza
May 15, 2004·Bioorganic & Medicinal Chemistry·Maykel Pérez González, Maria del Carmen Terán Moldes
Dec 5, 2014·Marine Drugs·Ri-Ming HuangYan Peng
Jan 6, 2018·Marine Drugs·Pablo A GarcíaMaría-Ángeles Castro

Related Concepts

Doridosine
Metazoa
Antihypertensive Agents
Diastolic Blood Pressure
Insula of Reil
Lentiform Nucleus Structure
Guanosine
Pulse Rate
Hemodynamics
Rats, Holtzman

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