Apadenoson (BMS-068645) is a selective adenosine 2A agonist that contains a methyl ester group which undergoes esterase hydrolysis to its acid metabolite. Apadenoson had been in phase III clinical trials by Forest (now a part of Allergan) for the treatment of coronary artery disease. However, this study has been terminated.

Midaxifylline, a potent and selective xanthine adenosine A1 receptor antagonist, was investigated for the treatment of Alzheimer's disease, cardiovascular disorders, kidney disorders, and major depressive disorder. However, all studies were discontinued.

Naxifylline [CVT 124, BG 9719], a small molecule diuretic, is one of a new class of potent and highly selective adenosine A1 receptor antagonists discovered at University of Florida. Naxifylline is an A1 adenosine receptor antagonist used for the treatment of edema associated with congestive heart failure. Naxifylline appears to be one of the more potent and clearly the most A1-selective antagonist reported to date, with K1 values of 0.67 and 0.45 nM, respectively, at the rat and cloned human A1-receptors and with 1800-fold (rat) and 2400-fold (human) subtype selectivity. Naxifylline protects against the decline in renal function observed with diuretic therapy by promoting urine output.

8-Cyclopentyl-1,3-dipropylxanthine (DPCPX) is a selective high-affinity antagonist radioligand for A1 adenosine receptors. DPCPX is a useful tool with which to explore the potential of activation of adenosine A1 receptors as an important mechanism in physiological and pathophysiological processes.

Preladenant (SCH-420814) is an adenosine A(2A) receptor antagonist with a high affinity and very high selectivity for adenosine A(2A) receptors, which is being developed by Merck & Co Inc (following its acquisition of Schering-Plough Corp) for the potential treatment of Parkinson's disease. Preladenant is a potent competitive antagonist of the human A2Areceptor (Ki = 1.1 nM) and has >1000-fold selectivity over all other adenosine receptors, making this compound the most selective A2A receptor antagonist reported to date. Preladenant was being researched as a potential treatment for Parkinson's disease. Positive results were reported in Phase II clinical trials in humans, but it did not prove itself to be more effective than a placebo during Phase III trials, and so was discontinued in May 2013.

Tecadenoson is a novel selective A1 adenosine receptor agonist that is currently being evaluated for the conversion of paroxysmal supraventricular tachycardia (PSVT) to sinus rhythm. Adenosine is a naturally occurring compound that stimulates all adenosine receptor subtypes in the body, including the A2 adenosine receptor which lowers blood pressure. In non-clinical trials, tecadenoson selectively stimulated the A1 adenosine receptor in the Atrioventricular node (AV node) and slowed the speed of electrical conduction across the AV node, reducing the number of electrical impulses that reached the ventricle, without affecting blood pressure. Clinical studies to date with intravenous tecadenoson suggest that it may slow the speed of AV nodal conduction by selectively stimulating the A1 adenosine receptor, and may avoid blood pressure lowering by not stimulating the A2 adenosine receptor. Thus, it may be possible to use intravenous tecadenoson to convert patients from PSVT to normal sinus rhythm without lowering blood pressure or causing adverse events related to vasodilation such as flushing, palpitations or a headache.

Cromakalim is an ATP-sensitive potassium (KATP) channel opener, which was studied for the treatment of gastric ulcer, hypertension and preventing a cardiomyopathy. But the development of this drug was discontinued due to heart lesions found in monkey chronic toxicity studies.