Acute administration of roflumilast enhances sensory gating in healthy young humans in a randomized trial

Psychopharmacology (Berl). 2018 Jan;235(1):301-308. doi: 10.1007/s00213-017-4770-y. Epub 2017 Nov 3.

Abstract

Introduction: Sensory 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.

Methods: The 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).

Results: Results 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.

Conclusion: The 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.

Keywords: Clinical trial; Phosphodiesterase; Phosphodiesterase inhibitor; Roflumilast; Sensory gating.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aminopyridines / adverse effects
  • Aminopyridines / pharmacology*
  • Animals
  • Benzamides / adverse effects
  • Benzamides / pharmacology*
  • Cyclopropanes / adverse effects
  • Cyclopropanes / pharmacology
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Electroencephalography / drug effects
  • Evoked Potentials, Auditory / drug effects
  • Female
  • Humans
  • Male
  • Nausea / etiology
  • Phosphodiesterase 4 Inhibitors / adverse effects
  • Phosphodiesterase 4 Inhibitors / pharmacology*
  • Sensory Gating / drug effects*
  • Vomiting / etiology
  • Young Adult

Substances

  • Aminopyridines
  • Benzamides
  • Cyclopropanes
  • Phosphodiesterase 4 Inhibitors
  • Roflumilast