A3 adenosine receptor allosteric modulator CF602 reverses erectile dysfunction in a diabetic rat model.

Adenosine plays a major role in erection by binding to its receptors and activating pathways resulting in increased arterial blood flow and intracavernosal pressure (ICP). CF602, an allosteric modulator of the A3 adenosine receptor (A3AR), increases the binding affinity of the endogenous adenosine to the receptor. We examined the effect of CF602 on resolving erectile dysfunction (ED) in a diabetic ED rat model (streptozotocin-induced diabetic rats that were screened for ED using the apomorphine test). ED was assessed by measuring ICP and main arterial pressure (MAP) during electrostimulation of the cavernosal nerve. A single dose of CF602 or placebo was applied either topically (100 μl from a 100 nM or 500 nM solution) or orally (100, 200 or 500 μg/kg) prior to erectile function assessment. A significant dose-dependent improvement in the ICP:MAP ratio without a change in MAP was recorded with the topical and oral CF602 treatments. A significant increase in smooth muscle:collagen ratio, vascular endothelial growth factor and endothelial nitric oxide synthase was also observed in both administration modes. In conclusion, topical and oral treatment with CF602 significantly improved erectile function, supporting its further evaluation as a treatment for ED.