The effects of the soluble guanylate cyclase stimulator riociguat on memory performance in healthy volunteers with a biperiden-induced memory impairment

Psychopharmacology (Berl). 2018 Aug;235(8):2407-2416. doi: 10.1007/s00213-018-4938-0. Epub 2018 Jun 7.


Rationale: After stimulation with nitric oxide, soluble guanylate cyclase (sGC) produces cyclic guanosine monophosphate (cGMP), which stimulates an important signalling pathway for long-term potentiation (LTP). By upregulating cGMP, LTP could be stimulated and thereby enhancing memory processes. The present study investigated the effects of the sGC stimulator riociguat on cognition in healthy volunteers. Participants were pre-treated with and without biperiden, which impairs memory performance, to investigate the memory-enhancing effects of riociguat.

Methods: Twenty volunteers participated in a double-blind placebo-controlled six-way crossover design with a cognitive test battery including the verbal learning task (VLT), n-back task, spatial memory test, the attention network test, and a reaction time task. Treatments were placebo and riociguat 0.5 mg, placebo and riociguat 1.0 mg, biperiden 2.0 mg and placebo, biperiden 2.0 mg and riociguat 0.5 mg and biperiden 2.0 mg and riociguat 1.0 mg.

Results: Blood pressure was found to be decreased and heart rate to be increased after administration of riociguat. Cognitive performance was not enhanced after administration of riociguat. Biperiden decreased episodic memory on the VLT, yet this deficit was not reversed by riociguat.

Conclusion: This supports the notion that biperiden might be a valuable pharmacological model to induce episodic memory impairments as observed in AD/MCI.

Keywords: Biperiden; Cognition; Episodic memory; Muscarinic receptors; cGMP; sGC stimulator.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Attention / drug effects
  • Biperiden / pharmacology
  • Blood Pressure / drug effects
  • Cognition / drug effects*
  • Cross-Over Studies
  • Double-Blind Method
  • Enzyme Activators / pharmacology*
  • Female
  • Guanylate Cyclase
  • Heart Rate / drug effects
  • Humans
  • Male
  • Memory / drug effects*
  • Memory Disorders / drug therapy*
  • Pyrazoles / pharmacology*
  • Pyrimidines / pharmacology*
  • Reaction Time / drug effects
  • Signal Transduction
  • Soluble Guanylyl Cyclase / pharmacology*
  • Verbal Learning / drug effects
  • Young Adult


  • Enzyme Activators
  • Pyrazoles
  • Pyrimidines
  • Biperiden
  • Guanylate Cyclase
  • Soluble Guanylyl Cyclase
  • riociguat