Novel l-adenosine analogs as cardioprotective agents.
Two l-nucleosides, l-3'-amino-3'-deoxy-N(6)-dimethyladenosine (l-3'-ADMdA) 1, previously synthesized in our laboratory, and the novel l-3'-amino-3'-deoxy-N(6)-methyladenosine-5'-N-methyluronamide (l-3'-AM-MECA) 2 were evaluated in an ischemia/reperfusion model on Langendorff perfused mouse heart. l-3'-ADMdA 1 was found to enhance functional recovery from ischemia (32.2+/-3.7cm H(2)O/s % rate pressure product, compared to 21.3+/-1.4 for the control and 30.7+/-3.4 for adenosine) and increase the time to onset of ischemic contracture (14.5+/-0.9min, compared to 10.5+/-1.0min for the control and 13.6+/-0.6min for adenosine) comparable to adenosine. Consistent with the functional recovery data, decreased infarction area was seen in the case of 1 (19.1+/-8.4, compared to 40.5+/-7.2% for the control and 11.5+/-2.1% for adenosine). In contrast, l-3'-AM-MECA 2 did not show significant functional recovery, increased onset of contracture, nor decreased infarction area compared to control. Unlike adenosine, neither 1 nor 2 induced cardiac standstill in mouse heart.
Kasiganesan
Harinath
H
Department of Pharmaceutical Sciences, College of Pharmacy, Medical University of South Carolina, 280 Calhoun Street, PO Box 250140, Charleston, SC 29425, USA.
Wright
Gary L
GL
Chiacchio
Maria Assunta
MA
Gumina
Giuseppe
G
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D002316:Cardiotonic Agents / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D051379:Mice; D009200:Myocardial Contraction / Q000187:drug effects; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000473:pathology
D002316:Cardiotonic Agents; D000241:Adenosine