Rolipram, an Antidepressant That Increases the Availability of cAMP, Transiently Enhances Wakefulness in Rats

The role of phosphodiesterase 4 in excessive daytime sleepiness in Parkinson's disease

“…Preclinical studies have provided evidence that phosphodiesterase 4 (PDE4) plays a role in daytime sleepiness [7][8][9][10]. PDE4 is an intracellular enzyme which hydrolyses cyclic adenosine monophosphate (cAMP), thus regulating signalling cascade including cAMP-protein kinase A (PKA)-cAMP response binding protein (CREB) [11].…”

“…Elevated cAMP/PKA signalling has recently been reported in the brain of an animal model of Huntington's disease (HD) animal models with sleep deficits [8]. Moreover, selective PDE4 inhibitors promote wakefulness [7]. Sleep deprivation has also been shown to increase PDE4 protein levels and activity in the hippocampus, subsequently reducing cAMP signalling and impairing hippocampal cAMP/PKA-dependent forms of synaptic plasticity [9].…”

Salubrinal, an inhibitor of protein synthesis, promotes deep slow wave sleep

“…ATF4 is a repressor of cAMP response element binding protein (CREB)-mediated gene expression (5). CREB activation facilitates waking in Drosophila (18), and increasing availability of cAMP increases wakefulness in rats (23). CREB mutant mice have reduced waking (13).…”

Innovative mechanisms of action for pharmaceutical cognitive enhancement: A systematic review

“…However, these drugs have multiple modes of action and produce only weak AMPA receptor activation and it is unclear how significant their ampakine actions are in producing their positive effects. Animal studies suggest memory and wakefulness enhancement properties of several racetams (Barad et al, 1998;Grossman et al, 2011;Lelkes et al, 1998;Mondadori et al, 1986;Samartgis et al, 2012;Scheuer et al, 1999;Trofimov et al, 2005;Tushmalova et al, 1995). It is noteworthy that animal experiments focused on restoring age-impaired cognitive functions (Gualtieri et al, 2002).…”