Tonapofylline: a selective adenosine-1 receptor antagonist for the treatment of heart failure.
BACKGROUND
The heart failure and cardiorenal syndromes are major public health hazards, affecting one in five persons during their lifetime. Alternatives to traditional loop-diuretics, including vasopressin and adenosine A(1) receptor antagonists are now in development.


METHODS
The pathophysiologic rationale for the use of tonapofylline, an intravenous and oral adenosine A(1) receptor antagonist, in patients with heart failure and/or the cardiorenal syndrome are reviewed. A comprehensive review of published literature describing its medicinal chemistry, pharmacokinetics, efficacy, safety and tolerability are provided. We searched the Medline/PubMed and Embase databases for the terms 'BG9928', 'tonapofylline', 'Adentri', 'adenosine', 'heart failure', 'renal failure' and 'cardiorenal syndrome' from 1 January 1992 to the present. References from pertinent manuscripts were also reviewed for additional relevant content.


RESULTS
The reader will better appreciate the potential role of tonapofylline in patients with heart failure and/or the cardiorenal syndrome. Additionally, the reader will gain an understanding of the current state of drug development and the rationale for the need for continued research.


CONCLUSIONS
Tonapofylline promotes natriuresis and diuresis, and may preserve glomerular filtration rate in patients with heart failure. Additionally, pilot data indicate that tonapofylline may be renoprotective in the setting of concomitant treatment with a loop-diuretic. Adverse effects were generally mild.
Ensor
Christopher R
CR
The Johns Hopkins Hospital, Comprehensive Transplant Center, Department of Pharmacy, 600 North Wolfe St., Carnegie 180, Baltimore, MD 21287-6180, USA.
Russell
Stuart D
SD
D058916:Adenosine A1 Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D002317:Cardiovascular Agents / Q000494:pharmacology / Q000627:therapeutic use*; D006333:Heart Failure / Q000188:drug therapy*; D006801:Humans; D014970:Xanthines / Q000494:pharmacology / Q000627:therapeutic use*
D058916:Adenosine A1 Receptor Antagonists; C505954:BG 9928; D002317:Cardiovascular Agents; D014970:Xanthines