The effects of the phosphodiesterase type 5 inhibitor vardenafil on cognitive performance in healthy adults: a behavioral- electroencephalography study

Abstract

Phosphodiesterase type 5 inhibitors (PDE5-Is) improve cognitive performance of rodents, but the few human studies investigating their effects did not systematically investigate cognitive effects and the results have been quite contradictory. Therefore, we examined whether the PDE5-I vardenafil improves memory and executive functioning and affect electroencephalography (EEG) in healthy young adults. Participants were selected out of a group of volunteers, based on their performance on a memory screening and they were orally treated with vardenafil (10-20 mg or placebo). Memory and executive functioning were tested while EEG activity was recorded. Additionally, a simple reaction time task and questionnaires addressing various complaints were presented. No prominent effects of vardenafil on cognition were found: participants only made more mistakes on a reaction time task after 20 mg vardenafil. During encoding of words, the P300 was generally smaller after vardenafil treatment. Furthermore, the N400 was larger after vardenafil 10 mg than placebo treatment in a spatial memory task at Fz. Finally, headache and feeling weak were reported more after vardenafil treatment. Vardenafil did not affect cognitive performance of healthy adults and showed only some incidental effects on ERPs. These findings in humans do not corroborate the cognition-enhancing effects of PDE5-Is in healthy animals.

Investigational phosphodiesterase inhibitors in phase I and phase II clinical trials for Alzheimer’s disease

“…Acute administration of a PDE5 inhibitor had no effects on cognition in healthy subjects [46,47,49]. Yet despite these negative findings we still cannot rule out inhibition of PDE5 as a treatment for cognitive impairment and/or AD.…”

“…verbal learning test) [48,49]. Memory and executive functioning were tested while EEG activity was recorded.…”

Rivastigmine but not vardenafil reverses cannabis-induced impairment of verbal memory in healthy humans

“…However, these tests are well established tests for studying human memory and should be sensitive enough to pick up any effects. Furthermore, the 20-mg dose of vardenafil used is comparable to effective doses in animals (Reneerkens et al 2013a). In previous studies with healthy non-impaired humans, a ceiling effect might also have attenuated any improved cognition/ memory performance.…”

The Role of NO/cGMP Signaling on Neuroinflammation: A New Therapeutic Opportunity

“…Clinical studies demonstrated that while a single dose of sildenafil does not cause a clear improvement in cognition in healthy adults [172], chronic administration of udenafil has shown to lead to an improvement in cognitive function [130]. This has led some to suggest that the therapeutic benefits of PDE5-Is may be better observed after chronic inhibition rather than after a single dose [173]. However, studies evaluating the anti-inflammatory effects of chronic PDE5-Is in PD models are lacking.…”