| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1 Department of Medicine, University of Florida, Gainesville, Florida 32610; and 2 CV Therapeutics, Palo Alto, California 94304
The use of full
agonists of the A1-adenosine receptor (A1-ADOR)
as antiarrhythmic agents is limited by their actions to cause high-grade atrioventricular (AV) block, profound bradycardia, atrial
fibrillation, and vasodilation. It may be possible to avoid these
undesired actions by use of partial agonists. We determined the effects
of CVT-2759, a potential partial agonist of A1-ADORs, on
guinea pig hearts. CVT-2759 (0.1-100 µM) increased the S-H interval of the isolated heart from 45 ± 1 to 60 ± 3 ms
(P < 0.01) with a half-maximal effect at 3.1 µM.
CVT-2759 did not cause second-degree AV block. CVT-2759 significantly
attenuated the actions of the full agonists
N6-cyclopentyladenosine and adenosine. CVT-2759
caused a moderate slowing of atrial rate by 
13% and did not shorten
the durations of either the atrial or the ventricular monophasic action
potential. Coronary conductance was increased by CVT-2759 only at
concentrations >10 µM. In contrast, CVT-2759 was a full agonist to
decrease cAMP content of rat adipocytes and Fischer rat thyroid line 5 cells. Results of radioligand binding assays indicated that CVT-2759 stabilized a high-affinity, G protein-coupled state of the
A1-ADOR in membranes prepared from rat adipocytes but not
in membranes prepared from the guinea pig brain. The results suggest
that a weak A1-ADOR agonist, such as CVT-2759, may be
useful to slow AV nodal conduction and thereby ventricular rate without
causing AV block, bradycardia, atrial arrhythmias, or vasodilation.
CVT-2759; FRTL-5; adipocyte; cyclopentyladenosine; iodotubercidin; atrioventricular
This article has been cited by other articles:
|
|
 |
|
  A. K. Dhalla, M. Y. Wong, P. J. Voshol, L. Belardinelli, and G. M. Reaven A1 adenosine receptor partial agonist lowers plasma FFA and improves insulin resistance induced by high-fat diet in rodents Am J Physiol Endocrinol Metab, May 1, 2007; 292(5): E1358 - E1363. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Fabritz, P. Kirchhof, L. Fortmuller, J. A Auchampach, H. A Baba, G. Breithardt, J. Neumann, P. Boknik, and W. Schmitz Gene dose-dependent atrial arrhythmias, heart block, and brady-cardiomyopathy in mice overexpressing A3 adenosine receptors Cardiovasc Res, June 1, 2004; 62(3): 500 - 508. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. N. Prystowsky, I. Niazi, A. B. Curtis, D. J. Wilber, T. Bahnson, K. Ellenbogen, A. Dhala, D. M. Bloomfield, M. Gold, A. Kadish, et al. Termination of paroxysmal supraventricular tachycardia by tecadenoson (CVT-510),a novel A1-adenosine receptor agonist J. Am. Coll. Cardiol., September 17, 2003; 42(6): 1098 - 1102. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Kirchhof, L. Fabritz, L. Fortmuller, G. P. Matherne, A. Lankford, H. A. Baba, W. Schmitz, G. Breithardt, J. Neumann, and P. Boknik Altered sinus nodal and atrioventricular nodal function in freely moving mice overexpressing the A1 adenosine receptor Am J Physiol Heart Circ Physiol, June 5, 2003; 285(1): H145 - H153. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Fraser, Z. Gao, M. J. Ozeck, and L. Belardinelli N-[3-(R)-Tetrahydrofuranyl]-6-aminopurine Riboside, an A1 Adenosine Receptor Agonist, Antagonizes Catecholamine-Induced Lipolysis without Cardiovascular Effects in Awake Rats J. Pharmacol. Exp. Ther., April 1, 2003; 305(1): 225 - 231. [Abstract] [Full Text]
|
|
|
|
 |
|
 Y. Song, L. Wu, J. C. Shryock, and L. Belardinelli Selective Attenuation of Isoproterenol-Stimulated Arrhythmic Activity by a Partial Agonist of Adenosine A1 Receptor Circulation, January 1, 2002; 105(1): 118 - 123. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
