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Xaliproden

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Title: Xaliproden  
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Subject: ATC code N07, 5-HT1A receptor, Tafamidis, RS-56812, MPPF
Collection: Abandoned Drugs, Naphthalenes, Organofluorides, Pyridines, Serotonin Receptor Agonists
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Xaliproden

Xaliproden
Systematic (IUPAC) name
1-[2-(2-naphthyl)ethyl]-4-[3-(trifluoromethyl)phenyl]-1,2,3,6-tetrahydropyridine
Clinical data
Legal status
?
Identifiers
CAS number  YesY
ATC code N07
PubChem
ChemSpider  N
UNII  YesY
KEGG  YesY
Chemical data
Formula C24H22F3N 
Mol. mass 381.433 g/mol
 N   

Xaliproden (codenamed SR57746) is a drug which acts as a 5HT1A agonist.[1] It has neurotrophic and neuroprotective effects in vitro,[2][3] and has been proposed for use in the treatment of several neurodegenerative conditions including amyotrophic lateral sclerosis (ALS)[4] and Alzheimer's disease.[5]

Development of xaliproden for these two indications was discontinued in 2007 following analysis of Phase III data. While the drug did show an effect on hippocampal volume (suggesting perhaps a slowing of cell loss), there was insufficient evidence for efficacy in counteracting Alzheimer's related cognitive decline. Similarly while there were some indicators of efficacy in ALS, including a small but clinically noteworthy effect on some functional parameters, the overall benefit did not reach statistical significance when results across several Phase III trials were averaged. Xaliproden remains under investigation for treatment of chemotherapy-induced peripheral neuropathy.[6][7]

References

  1. ^ Appert-Collin, A; Duong, FH; Passilly Degrace, P; Warter, JM; Poindron, P; Gies, JP (2005). "MAPK activation via 5-hydroxytryptamine 1A receptor is involved in the neuroprotective effects of xaliproden". International journal of immunopathology and pharmacology 18 (1): 21–31.  
  2. ^ Labie, C; Lafon, C; Marmouget, C; Saubusse, P; Fournier, J; Keane, PE; Le Fur, G; Soubrié, P (1999). "Effect of the neuroprotective compound SR57746A on nerve growth factor synthesis in cultured astrocytes from neonatal rat cortex".  
  3. ^ Duong, FH; Warter, JM; Poindron, P; Passilly, P (1999). "Effect of the nonpeptide neurotrophic compound SR 57746A on the phenotypic survival of purified mouse motoneurons". British Journal of Pharmacology 128 (7): 1385–92.  
  4. ^ Meininger, V; Bensimon, G; Bradley, WR; Brooks, B; Douillet, P; Eisen, AA; Lacomblez, L; Leigh, PN; Robberecht, W (2004). "Efficacy and safety of xaliproden in amyotrophic lateral sclerosis: results of two phase III trials". Amyotrophic lateral sclerosis and other motor neuron disorders : official publication of the World Federation of Neurology, Research Group on Motor Neuron Diseases 5 (2): 107–17.  
  5. ^ Lemaire L, Fournier J, Ponthus C, Le Fur Y, Confort-Gouny S, Vion-Dury J, Keane P, Cozzone P (2002). "Magnetic resonance imaging of the neuroprotective effect of xaliproden in rats". Invest Radiol 37 (6): 321–7.  
  6. ^ Susman, E (2006). "Xaliproden lessens oxaliplatin-mediated neuropathy". The lancet oncology 7 (4): 288.  
  7. ^ Wolf, S; Barton, D; Kottschade, L; Grothey, A; Loprinzi, C (2008). "Chemotherapy-induced peripheral neuropathy: prevention and treatment strategies". European journal of cancer (Oxford, England : 1990) 44 (11): 1507–15.  


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