Tonapofylline: a selective adenosine-1 receptor antagonist for the treatment of heart failure

Importance of the field: 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 A₁ receptor antagonists are now in development.

Areas covered in this review: The pathophysiologic rationale for the use of tonapofylline, an intravenous and oral adenosine A₁ 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.

What the reader will gain: 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.

Take home message: 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.