Abstract
IntroductionSensory gating is a process involved in early information processing which prevents overstimulation of higher cortical areas by filtering sensory information. Research has shown that the process of sensory gating is disrupted in patients suffering from clinical disorders including attention deficit hyper activity disorder, schizophrenia, and Alzheimer’s disease. Phosphodiesterase (PDE) inhibitors have received an increased interest as a tool to improve cognitive performance in both animals and man, including sensory gating.MethodsThe current study investigated the effects of the PDE4 inhibitor roflumilast in a sensory gating paradigm in 20 healthy young human volunteers (age range 18–30 years). We applied a placebo-controlled randomized cross-over design and tested three doses (100, 300, 1000 μg).ResultsResults show that roflumilast improves sensory gating in healthy young human volunteers only at the 100-μg dose. The effective dose of 100 μg is five times lower than the clinically approved dose for the treatment of acute exacerbations in chronic obstructive pulmonary disease (COPD). No side-effects, such as nausea and emesis, were observed at this dose. This means roflumilast shows a beneficial effect on gating at a dose that had no adverse effects reported following single-dose administration in the present study.ConclusionThe PDE4 inhibitor roflumilast has a favorable side-effect profile at a cognitively effective dose and could be considered as a treatment in disorders affected by disrupted sensory gating.
Highlights
Sensory gating is a process involved in early information processing which prevents overstimulation of higher cortical areas by filtering sensory information
The P50 has been suggested as a biomarker for the evaluation of drugs that may potentially have a beneficial effect on cognitive functions in Psychopharmacology (2018) 235:301–308 schizophrenia (Javitt et al 2008), but despite the prominent role that P50 abnormalities have played in our understanding of schizophrenia, more data is needed to fully incorporate P50 as clinical correlate (Potter et al 2006)
A PET study with the ligand [18F]B9302107 for roflumilast confirmed that the currently marketed dose for chronic obstructive pulmonary disease (COPD) is a brain penetrant in humans. On basis of this existing data, we investigated the effects of the PDE4 inhibitor roflumilast on sensory gating in humans
Summary
Sensory gating is a process involved in early information processing which prevents overstimulation of higher cortical areas by filtering sensory information. The P50 has been suggested as a biomarker for the evaluation of drugs that may potentially have a beneficial effect on cognitive functions in Psychopharmacology (2018) 235:301–308 schizophrenia (Javitt et al 2008), but despite the prominent role that P50 abnormalities have played in our understanding of schizophrenia, more data is needed to fully incorporate P50 as clinical correlate (Potter et al 2006). One advantage of this EEG-related measure is that it can be used for translational purposes (Blokland et al 2015)
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