Phosphodiesterase-4 regulates the intracellular level of cAMP.
Roflumilast, a selective
PDE-4 inhibitor was the first agent in this class to have reached the market for patients with
chronic obstructive pulmonary disease worldwide. Numerous preclinical evidences indicate the role of
PDE-4 inhibitors in reversal of ageing-related alterations induced in animal models by various pharmacological agents, overexpression of mutant forms of human
amyloid precursor
proteins and in aging, as well.
Roflumilast was capable of decreasing PDE-4B and 4D subtypes with an increase in the expression of pCREB and
BDNF in hippocampus of rats. The beneficial effects of
roflumilast on cognition are believed to be mediated through the above-mentioned cellular effects. Recently, Jabaris et al had shown that
roflumilast has improved the short and long-term memory in rodents. Several lines of evidence indicate that targeting PDE-4 inhibition might offer novel approaches in the treatment of age-associated memory impairment and in
Alzheimer's disease. Likewise, in a recent report,
roflumilast improved the memory functions in humans after administration of 100 μg of the
drug, without the typical side effects of
PDE-4 inhibitors, which might offer a novel therapeutic option for the treatment of
cognitive impairment and
Alzheimer disease. In the current article, the author reviews the most recent evidences demonstrating the beneficial effects of
roflumilast on learning and memory in animal models and humans.