A randomised trial of the effect of the glycine reuptake inhibitor Org 25935 on cognitive performance in healthy male volunteers

Hum Psychopharmacol. 2014 Mar;29(2):163-71. doi: 10.1002/hup.2384.

Abstract

Objective: Cognitive impairment is integral to many neurological illnesses. Specific enhancement of glutamatergic transmission may improve memory and learning. Org 25935 increases the synaptic availability of glycine, an obligate co-agonist with glutamate at N-methyl-D-aspartate receptors. We hypothesised that Org 25935 would acutely improve the learning and memory of healthy volunteers.

Methods: A randomised, double-blind, parallel-group, single-dose study of Org 25935 and placebo was carried out. Thirty-two healthy male volunteers took either 12-mg Org 25935 or matching placebo and were later assessed with the manikin task, digit span and verbal memory tests. Systematic assessments of cardiovascular and adverse events were also taken.

Results: There was no effect of Org 25935 on reaction time, number of correct responses or learning (greater or slower improvement over successive tasks) compared with placebo. Org 25935 caused significantly more dizziness and drowsiness compared with placebo; these side effects were mainly mild.

Conclusions: A single dose of Org 25935 does not improve learning or memory in healthy male individuals. However, the drug was well tolerated, and it remains to be seen whether it would have a positive effect on cognition in patient groups with pre-existing cognitive deficits.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Blood Pressure / drug effects
  • Cognition / drug effects*
  • Double-Blind Method
  • Electrocardiography
  • Heart / drug effects
  • Heart / physiology
  • Heart Rate / drug effects
  • Humans
  • Male
  • Memory / drug effects*
  • Middle Aged
  • Neuropsychological Tests
  • Neurotransmitter Uptake Inhibitors / adverse effects
  • Neurotransmitter Uptake Inhibitors / blood
  • Neurotransmitter Uptake Inhibitors / pharmacology*
  • Reaction Time
  • Task Performance and Analysis
  • Tetrahydronaphthalenes / adverse effects
  • Tetrahydronaphthalenes / blood
  • Tetrahydronaphthalenes / pharmacology*
  • Treatment Outcome
  • Young Adult

Substances

  • N-methyl-N-(6-methoxy-1-phenyl-1,2,3,4-tetrahydronaphthalen-2-ylmethyl)aminomethylcarboxylic acid
  • Neurotransmitter Uptake Inhibitors
  • Tetrahydronaphthalenes