A pilot open label, single dose trial of fenobam in adults with fragile X syndrome

Journal of Medical Genetics

Volumn 46, Issue 4, 2009, Pages 266-271

  Berry Kravis, E ^a   Hessl, D ^b,c   Coffey, S ^c,g   Hervey, C ^a   Schneider, A ^b,c   Yuhas, J ^b   Hutchison, J ^d   Snape, M ^d   Tranfaglia, M ^e   Nguyen, D V ^f   Hagerman, R ^c,g  

^a RUSH UNIVERSITY MEDICAL CENTER   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

^d Neuropharm Ltd   (United Kingdom)

^e FRAXA Research Foundation   (United States)

^f UNIVERSITY OF CALIFORNIA   (United States)

^g UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

FENOBAM; METABOTROPIC RECEPTOR ANTAGONIST; UNCLASSIFIED DRUG;

ADULT; ANXIETY; ARTICLE; ATTENTION; BLOOD ANALYSIS; CLINICAL ARTICLE; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DIZZINESS; DOSE RESPONSE; DRUG BLOOD LEVEL; DRUG DOSE ESCALATION; DRUG EFFECT; DRUG SAFETY; FEMALE; FRAGILE X SYNDROME; HUMAN; INHIBITION (PSYCHOLOGY); MALE; MAXIMUM PLASMA CONCENTRATION; MENTAL PERFORMANCE; OPEN STUDY; OUTCOME ASSESSMENT; PHENOTYPE; PILOT STUDY; PREPULSE INHIBITION; PRIORITY JOURNAL; SEDATION; SIDE EFFECT; SINGLE DRUG DOSE; TREATMENT RESPONSE; TREMOR; VITAL SIGN;

ADMINISTRATION, ORAL; ADOLESCENT; ADULT; CHROMATOGRAPHY, LIQUID; FEMALE; FRAGILE X SYNDROME; HUMANS; IMIDAZOLES; INHIBITION (PSYCHOLOGY); MALE; MASS SPECTROMETRY; NEURAL INHIBITION; NEUROPSYCHOLOGICAL TESTS; PILOT PROJECTS; RECEPTORS, METABOTROPIC GLUTAMATE; YOUNG ADULT;

ANIMALIA;

EID: 65949096495     PISSN: 00222593     EISSN: 14686244     Source Type: Journal    
DOI: 10.1136/jmg.2008.063701     Document Type: Article

References (29)

1. Hagerman PJ, The fragile X prevalence paradox. J Med Genet 2008;45:498-9.
2. Verkerk AJ, Pieretti M, Sutcliffe JS, Fu YH, Kuhl DP, Pizzuti A, Reiner O, Richards S, Victoria MF, Zhang FP, Eussen BE, van Ommen GJB, Blonden LA, Riggins GJ, Chastain JL, Kunst CB, Galjaard H, Caskey CT, Nelson DL, Oostra BA, Warren ST. Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome. Cell 1991;65:905-14.
3. Devys D, Lutz Y, Rouyer N, Bellocq JP, Mandel JL. The FMR-1 protein is cytoplasmic, most abundant in neurons and appears normal in carriers of a fragile X premutation. Nat Genet 1993;4:335-40.
4. Grossman AW, Aldridge GM, Weiler IJ, Greenough WT. Local protein synthesis and spine morphogenesis: fragile X syndrome and beyond. J Neurosci 2006;26:7151-5.
5. Antar LN, Afroz R, Dictenberg JB, Carroll RC, Bassell GJ. Metabotropic glutamate receptor activation regulates fragile X mental retardation protein and FMR1 mRNA localization differentially in dendrites and at synapses. J Neurosci 2004;24:2648-55.
6. Aschrafi A, Cunningham BA, Edelman GM, Vanderklish PW. The fragile X mental retardation protein and group I metabotropic glutamate receptors regulate levels of mRNA granules in brain. Proc Natl Acad Sci USA 2005;102:2180-5.
7. Weiler IJ, Spangler CC, Klintsova AY, Grossman AW, Kim SH, Bertaina-Anglade V, Khaliq H, de Vries FE, Lambers FA, Hatia F, Base CK, Greenough WT. Fragile X mental retardation protein is necessary for neurotransmitter-activated protein translation at synapses. Proc Natl Acad Sci USA 2004;101:17504-9.
8. Huber KM, Gallagher SM, Warren ST, Bear MF. Altered synaptic plasticity in a mouse model of fragile X mental retardation. Proc Natl Acad Sci USA 2002;99:7746-50.
9. Koekkoek SK, Yamaguchi K, Milojkovic BA, Dortland BR, Ruigrok TJ, Maex R, De Graaf W, Smit AE, VanderWerf F, Bakker CE, Willemsen R, Ikeda T, Kakizawa S, Onodera K, Nelson DL, Mientjes E, Joosten M, De Schutter E, Oostra BA, Ito M, De Zeeuw CI. Deletion of FMR1 in purkinje cells enhances parallel fiber LTD, enlarges spines, and attenuates cerebellar eyelid conditioning in fragile X syndrome. Neuron 2005;47:339-52.
10. Bear MF, Huber KM, Warren ST. The mGluR theory of fragile X mental retardation. Trends Neurosci 2004;27:370-7.
11. Irwin SA, Galvez R, Weiler IJ, Beckel-Mitchener A, Greenough WT. Brain structure and functions of FMR1 protein. In: Hagerman RJ, Hagerman PJ, eds. Fragile X syndrome: diagnosis, treatment and research, 3rd ed. Baltimore, Maryland: The Johns Hopkins University Press, 2002:191-205.
12. Beckel-Mitchener A, Greenough WT. Correlates across the structural, functional, and molecular phenotypes of fragile X syndrome. Ment Retard Dev Disabil Res Rev 2004;10:53-9.
13. Chuang SC, Zhao W, Bauchwitz R, Yan Q, Bianchi R, Wong RK. Prolonged epileptiform discharges induced by altered group I metabotropic glutamate receptormediated synaptic responses in hippocampal slices of a fragile X mouse model. J Neurosci 2005;25:8048-55.
14. Yan QJ, Rammal M, Tranfaglia M, Bauchwitz RP. Suppression of two major fragile X syndrome mouse model phenotypes by the mGluR5 antagonist MPEP. Neuropharmacology 2005;49:1053-66.
15. McBride SM, Choi CH, Wang Y, Liebelt D, Braunstein E, Ferreiro D, Sehgal A, Siwicki KK, Dockendorff TC, Nguyen HT, McDonald TV, Jongens TA. Pharmacological rescue of synaptic plasticity, courtship behavior, and mushroom body defects in a Drosophila model of fragile X syndrome. Neuron 2005;45:753-64.
16. Dölen G, Osterweil E, Rao BS, Smith GB, Auerbach BD, Chattarji S, Bear MF. Correction of fragile X syndrome in mice. Neuron 2007;56:955-62.
17. Porter RH, Jaeschke G, Spooren W, Ballard TM, Büttelmann B, Kolczewski S, Peters JU, Prinssen E, Wichmann J, Vieira E, Mühlemann A, Gatti S, Mutel V, Malherbe P. Fenobam: a clinically validated nonbenzodiazepine anxiolytic is a potent, selective, and noncompetitive mGlu5 receptor antagonist with inverse agonist activity. J Pharmacol Exp Ther 2005;315:711- 21.
18. Friedmann C, Davis L, Ciccone P, Rubin R. Phase II double-blind controlled study of a new anxiolytic, fenobam (McN-3377) vs placebo. Curr Ther Res 1980;27:144-51.
19. Pecknold JC, McClure DJ, Appeltauer L, Wrzesinski L, Allan T. Treatment of anxiety using fenobam (a nonbenzodiazepine) in a double-blind standard (diazepam) placebocontrolled study. J Clin Psychopharmacol 1982;2:129-33.
20. Itil TM, Seaman BA, Huque M, Mukhopadhyay S, Blasucci D, Nq KT, Ciccone PE. The clinical and quantitative EEG effects and plasma levels of fenbam (McN-3377) in subjects with anxiety: an open rising dose tolerance and efficacy study. Curr Ther Res 1978;24:708-24.
21. de Vrij FMS, Levenga J, van der Linde HC, Koekkoek SK, De Zeeuw CI, Nelson DL, Mientjes E, Oostra BA, Willemsen R. Rescue of behavioral phenotype and neuronal protrusion morphology in Fmr1 KO mice. Neurobiol Dis 2008;31:127-32.
22. Nakamoto M, Nalavadi V, Epstein MP, Narayanan U, Bassell GJ, Warren ST. Fragile X mental retardation protein deficiency leads to excessive mGluR5-dependent internalization of AMPA receptors. Proc Natl Acad Sci USA 2007;104:15537-42.
23. Frankland PW, Wang Y, Rosner B, Shimizu T, Balleine BW, Dykens EM, Ornitz EM, Silva AJ. Sensorimotor gating abnormalities in young males with fragile X syndrome and FMR1-knockout mice. Mol Psychiatry 2004;9:417-25.
24. Hessl D, Cordeiro L, Yuhas J, Campbell A, Ornitz E, Berry-Kravis E, Elizabeth Chruscinski E, Hervey C, Long JM, Hagerman RJ. Prepulse inhibition in fragile X syndrome: feasibility, reliability, and implications for treatment. Am J Med Genet B Neuropsychiatr Genet 2008 Sept 10. [Epub ahead of print]
25. Hawk Jr LW, Yartz AR, Pelham Jr WE, Lock TM. The effects of methylphenidate on prepulse inhibition during attended and ignored prestimuli among boys with attentiondeficit hyperactivity disorder. Psychopharmacology (Berl) 2003;165:118-27.
26. Minassian A, Feifel D, Perry W. The relationship between sensorimotor gating and clinical improvement in acutely ill schizophrenia patients. Schizophr res 2007;89:225-31.
27. Berry-Kravis E, Krause SE, Block SS, Guter S, Wuu J, Leurgans S, Decle P, Potanos K, Cook E, Salt J, Maino D, Weinberg D, Lara R, Jardini T, Cogswell J, Johnson SA, Hagerman R. Effect of CX516, an AMPA-modulating compound, on cognition and behavior in fragile X syndrome: a controlled trial. J Child Adolesc Psychopharmacol 2006;16:525-40.
28. Sullivan K, Hooper S, Hatton D. Behavioural equivalents of anxiety in children with fragile X syndrome: parent and teacher report. J Intellect Disabil Res 2007;51:54-65.
29. Berry-Kravis E, Sumis A, Kim OK, Lara R, Wuu J. Characterization of potential outcome measures for future clinical trials in fragile X syndrome. J Autism Dev Disord 2008;38:1751-7.