Effect of CX516, an AMPA-modulating compound, on cognition and behavior in fragile X syndrome: a controlled trial

J Child Adolesc Psychopharmacol. 2006 Oct;16(5):525-40. doi: 10.1089/cap.2006.16.525.


A Phase II, 4-week randomized, double-blind, placebo-controlled clinical trial was conducted to evaluate the safety and efficacy of the Ampakine compound CX516 as a potential treatment for the underlying disorder in fragile X syndrome (FXS). After baseline screening, subjects with FXS (n = 49) underwent a 1-week placebo lead-in and then were randomized to study drug or placebo for a 4-week period. Cognitive and behavioral outcome measures were administered prior to treatment, at the end of treatment, and 2 weeks posttreatment. There were minimal side effects, no significant changes in safety parameters, and no serious adverse events. There was a 12.5% frequency of allergic rash in the CX516 group and 1 subject developed a substantial rash. There was also no significant improvement in memory, the primary outcome measure, or in secondary measures of language, attention/executive function, behavior, and overall functioning in CX516-treated subjects compared to placebo. This study did demonstrate that many outcome measures were reproducible in this test-retest setting for the FXS population, yet some were too difficult or variable. Adult subjects with FXS were able to complete an intensive clinical trial, and some valid outcome measures were identified for future FXS trial design. Problems with potency of CX516 in other studies have suggested dosing may have been inadequate for therapeutic effect and thus it remains unclear whether modulation of AMPA-mediated neurotransmission is a viable therapeutic strategy for the treatment of FXS.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Autistic Disorder / drug therapy
  • Autistic Disorder / psychology
  • Child Behavior Disorders / drug therapy*
  • Child Behavior Disorders / psychology
  • Cognition Disorders / drug therapy*
  • Cognition Disorders / psychology
  • Dioxoles / adverse effects
  • Dioxoles / therapeutic use*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Eruptions / etiology
  • Female
  • Fragile X Syndrome / drug therapy*
  • Fragile X Syndrome / psychology
  • Humans
  • Long-Term Potentiation / drug effects
  • Male
  • Neuronal Plasticity / drug effects
  • Neuropsychological Tests
  • Personality Assessment
  • Piperidines / adverse effects
  • Piperidines / therapeutic use*
  • Receptors, AMPA / drug effects*
  • Synaptic Transmission / drug effects
  • Treatment Outcome


  • 1-(quinoxalin-6-ylcarbonyl)piperidine
  • Dioxoles
  • Piperidines
  • Receptors, AMPA