Trabodenoson is a potent (Ki = 0.97 nM) and selective (>10,000- fold vs. adenosine 2 receptor) adenosine 1 receptor agonist. Ex vivo, trabodenoson (100 nM to 3 uM) progressively prolonged A-V-nodal conduction without reducing left ventricular function or coronary resistance. In vivo, trabodenoson up to a dose of 50 ug/kg did not reduce the carotid arterial blood pressure. Twice-daily ocular doses of trabodenoson, from 50 to 500 ug, were well tolerated and showed a dose-related decrease in intraocular pressure that was statistically significant and clinically relevant at 500 ug in patients with ocular hypertension or primary open-angle glaucoma. Trabodenoson had been in phase III clinical trial for the treatment of glaucoma and ocular hypertension. However, this development was discontinued.

Tozadenant (SYN115) is an adenosine A2A receptor antagonist initially developed for treatment of Parkinson's disease but may also have utility in other CNS disorders. A2a receptors are expressed in high concentration in the striatum of the brain and play an important role in regulating motor function. Tozadenant blocks the effect of endogenous adenosine at the A2a receptors, resulting in the potentiation of the effect of dopamine at the D2 receptor and inhibition of the effect of glutamate at the mGluR5 receptor. This enables restoration of motor function in Parkinson’s disease. Tozadenant has the potential for use as mono-therapy or adjunctive therapy in combination with L-Dopa and dopamine agonists for the treatment of the motor and non-motor symptoms associated with Parkinson’s disease. may also have neuroprotective effects, which raises the possibility that it could slow the deterioration of dopamine producing cells and modify disease progression. As was reported in international, multicentre, phase 2b, randomised, double-blind, placebo-controlled, parallel-group, dose-finding clinical trial of tozadenant in levodopa-treated patients with Parkinson's disease who had motor fluctuations tozadenant at 120 or 180 mg twice daily was generally well tolerated and was effective at reducing off-time.

UK-432097 is a selective adenosine A2a agonist which was in development with Pfizer as an inhaled treatment for asthma and chronic obstructive pulmonary disease. UK-432097 had been in phase II clinical trials by Pfizer for the treatment of chronic obstructive pulmonary disease (COPD). However, this study was terminated prematurely due to futility based on results of interim analysis.

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.