Fasoracetam in adolescents with ADHD and glutamatergic gene network variants disrupting mGluR neurotransmitter signaling

Nat Commun. 2018 Jan 16;9(1):4. doi: 10.1038/s41467-017-02244-2.


The glutamatergic neurotransmitter system may play an important role in attention-deficit hyperactivity disorder (ADHD). This 5-week, open-label, single-blind, placebo-controlled study reports the safety, pharmacokinetics and responsiveness of the metabotropic glutamate receptor (mGluR) activator fasoracetam (NFC-1), in 30 adolescents, age 12-17 years with ADHD, harboring mutations in mGluR network genes. Mutation status was double-blinded. A single-dose pharmacokinetic profiling from 50-800 mg was followed by a single-blind placebo at week 1 and subsequent symptom-driven dose advancement up to 400 mg BID for 4 weeks. NFC-1 treatment resulted in significant improvement. Mean Clinical Global Impressions-Improvement (CGI-I) and Severity (CGI-S) scores were, respectively, 3.79 at baseline vs. 2.33 at week 5 (P < 0.001) and 4.83 at baseline vs. 3.86 at week 5 (P < 0.001). Parental Vanderbilt scores showed significant improvement for subjects with mGluR Tier 1 variants (P < 0.035). There were no differences in the incidence of adverse events between placebo week and weeks on active drug. The trial is registered at https://clinicaltrials.gov/ct2/show/study/NCT02286817 .

Publication types

  • Controlled Clinical Trial
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Area Under Curve
  • Attention Deficit Disorder with Hyperactivity / drug therapy*
  • Attention Deficit Disorder with Hyperactivity / genetics
  • Child
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Excitatory Amino Acid Agents / administration & dosage
  • Excitatory Amino Acid Agents / adverse effects
  • Excitatory Amino Acid Agents / pharmacokinetics
  • Excitatory Amino Acid Agents / therapeutic use*
  • Female
  • Half-Life
  • Humans
  • Male
  • Mutation
  • Receptors, Metabotropic Glutamate / drug effects
  • Receptors, Metabotropic Glutamate / genetics*
  • Single-Blind Method


  • Excitatory Amino Acid Agents
  • Receptors, Metabotropic Glutamate

Associated data

  • ClinicalTrials.gov/NCT02286817