The Full Wiki

More info on Fenobam

Fenobam: Wikis

Advertisements

Note: Many of our articles have direct quotes from sources you can cite, within the Wikipedia article! This article doesn't yet, but we're working on it! See more info or our list of citable articles.

Encyclopedia

From Wikipedia, the free encyclopedia

Fenobam
Fenobam.svg
IUPAC name
Identifiers
CAS number 57653-26-6
PubChem 162834
MeSH fenobam
SMILES
Properties
Molecular formula C11H11ClN4O2
Molar mass 266.684
Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

Fenobam is an imidazole derivative which was developed by McNeil Laboratories in the late 1970s, as a novel anxiolytic drug with an at the time unidentified molecular target in the brain. Subsequently it was found that fenobam acts as a potent and selective negative allosteric modulator of the metabotropic glutamate receptor subtype mGluR5,[1][2] and it has been used as a lead compound for the development of a range of newer mGluR5 antagonists.[3][4][5]

Fenobam has anxiolytic effects comparable to those of benzodiazepine drugs,[6][7][1] but was never commercially marketed for the treatment of anxiety due to dose-limiting side effects such as amnesia and psychotomimetic symptoms.[8][9] Following the discovery of its activity as a potent negative allosteric modulator of mGluR5, fenobam has been re-investigated for many applications, with its profile of combined antidepressant, anxiolytic, analgesic and anti-addictive effects potentially useful given the common co-morbidity of these symptoms.[10][11] It has also shown promising initial results in the treatment of Fragile X syndrome.[12]

References

  1. ^ a b Porter RH, Jaeschke G, Spooren W, et al (November 2005). "Fenobam: a clinically validated nonbenzodiazepine anxiolytic is a potent, selective, and noncompetitive mGlu5 receptor antagonist with inverse agonist activity". J. Pharmacol. Exp. Ther. 315 (2): 711–21. doi:10.1124/jpet.105.089839. PMID 16040814.  
  2. ^ Marino MJ, Conn PJ. Glutamate-based therapeutic approaches: allosteric modulators of metabotropic glutamate receptors. Current Opinion in Pharmacology. 2006 Feb;6(1):98-102. PMID 16368268
  3. ^ Wållberg A, Nilsson K, Osterlund K, Peterson A, Elg S, Raboisson P, Bauer U, Hammerland LG, Mattsson JP. Phenyl ureas of creatinine as mGluR5 antagonists. A structure-activity relationship study of fenobam analogues. Bioorganic and Medicinal Chemistry Letters. 2006 Mar 1;16(5):1142-5. PMID 16380255
  4. ^ Ceccarelli SM, Jaeschke G, Buettelmann B, Huwyler J, Kolczewski S, Peters JU, Prinssen E, Porter R, Spooren W, Vieira E. Rational design, synthesis, and structure-activity relationship of benzoxazolones: new potent mglu5 receptor antagonists based on the fenobam structure. Bioorganic and Medicinal Chemistry Letters. 2007 Mar 1;17(5):1302-6. PMID 17189691
  5. ^ Jaeschke G, Porter R, Büttelmann B, Ceccarelli SM, Guba W, Kuhn B, Kolczewski S, Huwyler J, Mutel V, Peters JU, Ballard T, Prinssen E, Vieira E, Wichmann J, Spooren W. Synthesis and biological evaluation of fenobam analogs as mGlu5 receptor antagonists. Bioorganic and Medicinal Chemistry Letters. 2007 Mar 1;17(5):1307-11. PMID 17196387
  6. ^ Pecknold JC, McClure DJ, Appeltauer L, Wrzesinski L, Allan T. Treatment of anxiety using fenobam (a nonbenzodiazepine) in a double-blind standard (diazepam) placebo-controlled study. Journal of Clinical Psychopharmacology. 1982 Apr;2(2):129-33. PMID 7042771
  7. ^ Goldberg ME, Salama AI, Patel JB, Malick JB. Novel non-benzodiazepine anxiolytics. Neuropharmacology. 1983 Dec;22(12B):1499-504. PMID 6142427
  8. ^ Palucha A, Pilc A. Metabotropic glutamate receptor ligands as possible anxiolytic and antidepressant drugs. Pharmacology and Therapeutics. 2007 Jul;115(1):116-47. PMID 17582504
  9. ^ Jacob W, Gravius A, Pietraszek M, Nagel J, Belozertseva I, Shekunova E, Malyshkin A, Greco S, Barberi C, Danysz W (May 2009). "The anxiolytic and analgesic properties of fenobam, a potent mGlu5 receptor antagonist, in relation to the impairment of learning". Neuropharmacology. doi:10.1016/j.neuropharm.2009.04.011. PMID 19426746.  
  10. ^ Carroll FI. Antagonists at metabotropic glutamate receptor subtype 5: structure activity relationships and therapeutic potential for addiction. Annals of the New York Academy of Sciences. 2008 Oct;1141:221-32. PMID 18991960
  11. ^ Montana MC, Cavallone LF, Stubbert KK, Stefanescu AD, Kharasch ED, Gereau RW (June 2009). "The mGlu5 antagonist fenobam is analgesic and has improved in vivo selectivity as compared to the prototypical antagonist MPEP". The Journal of Pharmacology and Experimental Therapeutics. doi:10.1124/jpet.109.154138. PMID 19515968.  
  12. ^ Berry-Kravis EM, Hessl D, Coffey S, Hervey C, Schneider A, Yuhas J, Hutchison J, Snape M, Tranfaglia M, Nguyen DV, Hagerman R. A pilot open-label single-dose trial of fenobam in adults with fragile X syndrome. Journal of Medical Genetics. 2009 Jan 6. PMID 19126569
Advertisements

Advertisements






Got something to say? Make a comment.
Your name
Your email address
Message