Fenobam: Difference between revisions

| ImageSize = 240px

| IUPACName = 1-(3-chlorophenyl)-3-(3-methyl-5-oxo-4H-imidazol-2-yl)urea

| OtherNames =

| CASNo = 57653-26-6

| PubChem = 162834

| IUPHAR_ligand = 1434

| SMILES = CN1CC(=O)N=C1NC(=O)NC2=CC(=CC=C2)Cl

| MeSHName = fenobam

| Formula = C₁₁H₁₁ClN₄O₂

| MolarMass = 266.684

| Appearance =

| Density =

| MeltingPt =

| BoilingPt =

| Solubility =

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| FlashPt =

| Autoignition =

'''Fenobam''' is an [[imidazole]] derivative 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 determined that fenobam acts as a [[Potency (pharmacology)|potent]] and [[selective]] [[negative allosteric modulator]] of the [[metabotropic glutamate receptor]] subtype [[Metabotropic glutamate receptor 5|mGluR₅]],<ref name="pmid16040814">{{cite journal |author=Porter RH, Jaeschke G, Spooren W, ''et al'' |title=Fenobam: a clinically validated nonbenzodiazepine anxiolytic is a potent, selective, and noncompetitive mGlu5 receptor antagonist with inverse agonist activity |journal=J. Pharmacol. Exp. Ther. |volume=315 |issue=2 |pages=711–21 |year=2005 |month=November |pmid=16040814 |doi=10.1124/jpet.105.089839 |url=}}</ref><ref>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</ref> and it has been used as a [[lead compound]] for the development of a range of newer mGluR₅ antagonists.<ref>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</ref><ref>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</ref><ref>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</ref>

Fenobam has anxiolytic effects comparable to those of [[benzodiazepine]] drugs,<ref>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</ref><ref>Goldberg ME, Salama AI, Patel JB, Malick JB. Novel non-benzodiazepine anxiolytics. ''Neuropharmacology''. 1983 Dec;22(12B):1499-504. PMID 6142427</ref><ref name="pmid16040814"/> but was never commercially marketed for the treatment of anxiety due to dose-limiting side effects such as amnesia and psychotomimetic symptoms.<ref>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</ref><ref name="pmid19426746">{{cite journal |author=Jacob W, Gravius A, Pietraszek M, Nagel J, Belozertseva I, Shekunova E, Malyshkin A, Greco S, Barberi C, Danysz W |title=The anxiolytic and analgesic properties of fenobam, a potent mGlu5 receptor antagonist, in relation to the impairment of learning |journal=Neuropharmacology |volume= 57|issue= 2|pages= 97–108|year=2009 |month=May |pmid=19426746 |doi=10.1016/j.neuropharm.2009.04.011 |url=}}</ref> 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.<ref>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</ref><ref name="pmid19515968">{{cite journal |author=Montana MC, Cavallone LF, Stubbert KK, Stefanescu AD, Kharasch ED, Gereau RW |title=The mGlu5 antagonist fenobam is analgesic and has improved in vivo selectivity as compared to the prototypical antagonist MPEP |journal=The Journal of Pharmacology and Experimental Therapeutics |volume= 330|issue= 3|pages= 834–43|year=2009 |month=June |pmid=19515968 |doi=10.1124/jpet.109.154138 |url= |pmc=2729799}}</ref> It has also shown promising initial results in the treatment of [[Fragile X syndrome]].<ref>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</ref>

Fenobam can be prepared in a two-step sequence from [[creatine]].<ref>Rasmussen, C. R.; 1976, {{US Patent|3983135}}.</ref>

[[File:Fenobam.png|500px]]

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{{glutamate_receptor_ligands}}

{{Anxiolytics}}

[[Category:Organochlorides]]