PDE6Aα Inhibitors

PDE6Aα inhibitors encompass a diverse range of compounds primarily targeting the phosphodiesterase enzyme family, which is responsible for breaking down cyclic nucleotides. PDE6A, in particular, is involved in the hydrolysis of cGMP in the retina, playing a pivotal role in phototransduction. The inhibitors of this enzyme mainly work by preventing the breakdown of cGMP, thereby increasing its levels in retinal cells. This elevation of cGMP is crucial as it affects photoreceptor cell function, dictating light response dynamics.

The majority of compounds mentioned, such as Sildenafil and Vardenafil, are primarily known for their inhibition of PDE5 but also show significant activity against PDE6A. This dual action ensures increased cGMP levels in both vascular and retinal tissues. Some compounds, like Zaprinast, are more direct in their PDE6A inhibitory action. In contrast, others, like Cilostazol or Anagrelide, primarily inhibit different PDE isoforms but could exert indirect effects on the cGMP pathway, subsequently influencing PDE6A function.