ABSTRACT
A few studies have reported that PDE-5-selective inhibitors possess neural effects. Hallen et al. reported that vardenafil, sildenafil, and tadalafil blunted release of NO from neurons in rabbit isolated corpus cavernosal tissue. 18 It was suggested that this could be protective against excessive smooth muscle relaxation leading to priapism; whether this effect is mediated via inhibition of neuronal PDE-5 and cGMP elevation is unclear. Reports of PDE-5-selective inhibitor effects on the central nervous system were initially met with skepticism because the inhibitors were not believed to cross the bloodbrain barrier, and it was conjectured that improved blood flow to certain brain regions could account for the results. However, reports of such effects on central nerves continue to accumulate in studies using both animal models and humans. Zhang et al. demonstrated that sildenafil or tadalafil administration in rats improves recovery from stroke, an effect that could be due to improved blood flow; however, sildenafil also improves survival of neuronal cells in culture. 19 Improved object recognition memory and memory consolidation following administration of PDE-selective inhibitors were reported. 20 Results of studies in hamsters indicated that sildenafil is effective in rapid adjustment of the circadian clock. 21 The mechanism or mechanisms mediating these processes is not known.
