A pilot open label, single dose trial of fenobam in adults with fragile X syndrome
Open accessAbstract
Objective: A pilot open label, single dose trial of fenobam, an mGluR5 antagonist, was conducted to provide an initial evaluation of safety and pharmacokinetics in adult males and females with fragile X syndrome (FXS). Methods: Twelve subjects, recruited from two fragile X clinics, received a single oral dose of 50–150 mg of fenobam. Blood for pharmacokinetic testing, vital signs and side effect screening was obtained at baseline and numerous time points for 6 h after dosing. Outcome measures included prepulse inhibition (PPI) and a continuous performance test (CPT) obtained before and after dosing to explore the effects of fenobam on core phenotypic measures of sensory gating, attention and inhibition. Results: There were no significant adverse reactions to fenobam administration. Pharmacokinetic analysis showed that fenobam concentrations were dose dependent but variable, with mean (SEM) peak values of 39.7 (18.4) ng/ml at 180 min after the 150 mg dose. PPI met a response criterion of an improvement of at least 20% over baseline in 6 of 12 individuals (4/6 males and 2/6 females). The CPT did not display improvement with treatment due to ceiling effects. Conclusions: Clinically significant adverse effects were not identified in this study of single dose fenobam across the range of dosages utilised. The positive effects seen in animal models of FXS treated with fenobam or other mGluR5 antagonists, the apparent lack of clinically significant adverse effects, and the potential beneficial clinical effects seen in this pilot trial support further study of the compound in adults with FXS.
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Fenobam tested in adults with fragile X syndrome produced beneficial effects including reduced anxiety and hyperarousal, improved prepulse inhibition of startle, and better accuracy on a continuous performance task.
“Fenobam, used in the past for anxiety treatment (109), was recently tested in adults with FXS (37).Beneficial effects such as reduced anxiety and hyperarousal, improved prepulse inhibition of startle, and better accuracy on a continuous performance task were also reported.”
From Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics (2012) · cites this paper as [37]
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- Authors
- Berry-Kravis, E., Hessl, D., Coffey, S., Hervey, C., Schneider, A., Yuhas, J., Hutchison, J., Snape, M., Tranfaglia, M., Nguyen, D. V., & Hagerman, R.
- Affiliations
- University of California Davis Medical Center (US)
- Rush University Medical Center (US)
- University of California, Davis (US)
- Fraxa Research Foundation (US)
- Venue
- Journal of Medical Genetics
- Publisher
- BMJ
- Published
- 2009-01-06
- Volume
- 46
- Issue
- 4
- Pages
- 266-271
- ISSN
- 0022-2593 (ISSN-L)
- 1468-6244
- PMC
- PMC2658751
- OpenAlex
- W2125608178
- Cited by
- 411
- References
- 28
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 6 · 2023: 3 · 2022: 10 · 2021: 10 · 2020: 8 · 2019: 8 · 2018: 14 · 2017: 21 · 2016: 19 · 2015: 21 · 2014: 43 · 2013: 46 · 2012: 47
- FWCI
- 38.58
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- Journal of Medical Genetics (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Funders
- FRAXA Research Foundation
- National Institutes of Health (90DD0596, RR024146)
- Centers for Disease Control and Prevention (U50DD000596)
- National Institute on Aging (RL1AG032119, RL1AG032115)
- National Institute of Mental Health (MH77554, K23MH077554)
- National Institute of Dental and Craniofacial Research (UL1DE019583)
- National Center for Research Resources (RR-024146, HD036071, 90DD0596, UL1RR024146)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD036071, R01HD036071)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Keywords
- fenobam, fragile X syndrome, mGluR5 antagonist, pharmacokinetics, safety, prepulse inhibition, sensory gating, attention, inhibition, adults, single-dose administration
- MeSH terms
- Administration, Oral, Adolescent, Adult, Chromatography, Liquid, Female, Fragile X Syndrome, Humans, Imidazoles, Inhibition, Psychological, Male, Neural Inhibition, Neuropsychological Tests, Pilot Projects, Mass Spectrometry, Receptors, Metabotropic Glutamate, Young Adult, Receptor, Metabotropic Glutamate 5
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