Sildenafil Improves Performance...

...cognitive performance, that is.

Sildenafil (aka Viagra) not only reduces jet lag in hamsters (Agostino et al., 2007), now it's been shown to improve object retrieval performance in monkeys (Rutten et al., 2007). Sildenafil is in the class of drugs known as phosphodiesterase inhibitors (PDEs). As indicated by the name, PDE drugs block phosphodiesterase, thereby preventing the degradation of cAMP and cGMP. Sildenafil inhibits the PDE5 subtype, whereas rolipram inhibits the PDE4 subtype.

Both drugs were equally effective in improving the monkeys' ability to correctly reach a food treat in a transparent box with one open side, which was billed as a prefrontal "executive function" task.

During vehicle sessions, monkeys readily reached for the food treats, successfully acquiring the treat on the first reach 100 ± 0% during easy trials and 52 ± 3% during difficult trials. Over the course of the experiment (2 months), there were no changes in vehicle performance.

The PDE4 inhibitor rolipram (0.003–0.1 mg/kg, i.m.) dose-dependently increased correct first reaches during difficult trials, reaching significance at 0.01 mg/kg. At the highest dose tested without side effects (0.03 mg/kg), the percentage correct first reaches were increased approximately 20 to 71 ± 3%.

The PDE5 inhibitor sildenafil (0.3–3 mg/kg, i.m.) dose-dependently increased correct first reaches during difficult trials, reaching significance at 1 mg/kg. At the highest dose tested (3 mg/kg), correct reaches were increased approximately 20 to 73 ± 3%. No side effects were observed.

Neither rolipram nor sildenafil altered performance during the easy trials, with the exception of the high dose of rolipram (0.1 mg/kg), in which monkeys failed to perform the task (data not shown) because of emetic side effects.

The mechanism(s) by which these PDE drugs might improve functioning of the prefrontal cortex are not well-elucidated at this point.

References

Agostino PV, Plano SA, Golombek DA. (2007). Sildenafil accelerates reentrainment of circadian rhythms after advancing light schedules. PNAS 104: 9834–9839.

Rutten K, Basile JL, Prickaerts J, Blokland A, Vivian JA. (2007).
Selective PDE inhibitors rolipram and sildenafil improve object retrieval performance in adult cynomolgus macaques. Psychopharmacology, Nov 23; [Epub ahead of print].