A pilot open label, single dose trial of fenobam in adults with fragile X syndrome
| Autor: | Jennifer Yuhas, Randi J Hagerman, Danh V. Nguyen, Andrea Schneider, Crystal Hervey, Michael Tranfaglia, Elizabeth Berry-Kravis, Julie A Hutchison, David R Hessl, Michael Snape, Sarah M. Coffey |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Adult
Male Dose Side effect Adolescent Receptor Metabotropic Glutamate 5 Administration Oral Pilot Projects Pharmacology Neuropsychological Tests Receptors Metabotropic Glutamate Mass Spectrometry 03 medical and health sciences chemistry.chemical_compound Young Adult 0302 clinical medicine Pharmacokinetics Genetics medicine Mavoglurant Humans Dosing Adverse effect Genetics (clinical) 030304 developmental biology 0303 health sciences Fenobam business.industry Imidazoles Neural Inhibition Original Articles medicine.disease 3. Good health Fragile X syndrome Inhibition Psychological chemistry Fragile X Syndrome Female business 030217 neurology & neurosurgery Chromatography Liquid |
| Zdroj: | Journal of Medical Genetics Berry-Kravis, E; Hessl, D; Coffey, S; Hervey, C; Schneider, A; Yuhas, J; et al.(2009). A pilot open label, single dose trial of fenobam in adults with fragile X syndrome. Journal of Medical Genetics, 46(4), 266-271. doi: 10.1136/jmg.2008.063701. UC Irvine: Retrieved from: http://www.escholarship.org/uc/item/4n84s2qk |
| ISSN: | 1468-6244 |
| DOI: | 10.1136/jmg.2008.063701. |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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