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Xaliproden

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Xaliproden
Clinical data
ATC code
Identifiers
  • 1-[2-(2-naphthyl)ethyl]-4-[3-(trifluoromethyl)phenyl]-1,2,3,6-tetrahydropyridine
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC24H22F3N
Molar mass381.442 g·mol−1
3D model (JSmol)
  • FC(F)(F)c4cccc(/C3=C/CN(CCc2cc1ccccc1cc2)CC3)c4
  • InChI=1S/C24H22F3N/c25-24(26,27)23-7-3-6-22(17-23)20-11-14-28(15-12-20)13-10-18-8-9-19-4-1-2-5-21(19)16-18/h1-9,11,16-17H,10,12-15H2 ☒N
  • Key:WJJYZXPHLSLMGE-UHFFFAOYSA-N ☒N
 ☒NcheckY (what is this?)  (verify)

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]

Paliroden was also explored as a treatment for people living with dementia.[8]

References

[edit]
  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. doi:10.1177/039463200501800104. PMID 15698508. S2CID 43254260.
  2. ^ Labie C, Lafon C, Marmouget C, Saubusse P, Fournier J, Keane PE, et al. (May 1999). "Effect of the neuroprotective compound SR57746A on nerve growth factor synthesis in cultured astrocytes from neonatal rat cortex". British Journal of Pharmacology. 127 (1): 139–144. doi:10.1038/sj.bjp.0702545. PMC 1566010. PMID 10369466.
  3. ^ Duong FH, Warter JM, Poindron P, Passilly P (December 1999). "Effect of the nonpeptide neurotrophic compound SR 57746A on the phenotypic survival of purified mouse motoneurons". British Journal of Pharmacology. 128 (7): 1385–1392. doi:10.1038/sj.bjp.0702910. PMC 1571767. PMID 10602316.
  4. ^ Meininger V, Bensimon G, Bradley WR, Brooks B, Douillet P, Eisen AA, et al. (June 2004). "Efficacy and safety of xaliproden in amyotrophic lateral sclerosis: results of two phase III trials". Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders. 5 (2): 107–117. doi:10.1080/14660820410019602. PMID 15204012. S2CID 2736180.
  5. ^ Lemaire L, Fournier J, Ponthus C, Le Fur Y, Confort-Gouny S, Vion-Dury J, et al. (June 2002). "Magnetic resonance imaging of the neuroprotective effect of xaliproden in rats". Investigative Radiology. 37 (6): 321–327. doi:10.1097/00004424-200206000-00003. PMID 12021588. S2CID 32239136.
  6. ^ Susman E (April 2006). "Xaliproden lessens oxaliplatin-mediated neuropathy". The Lancet. Oncology. 7 (4): 288. doi:10.1016/S1470-2045(06)70639-8. PMID 16598880.
  7. ^ Wolf S, Barton D, Kottschade L, Grothey A, Loprinzi C (July 2008). "Chemotherapy-induced peripheral neuropathy: prevention and treatment strategies". European Journal of Cancer. 44 (11): 1507–1515. doi:10.1016/j.ejca.2008.04.018. PMID 18571399.
  8. ^ Labie C, Canolle B, Chatelin S, Lafon C, Fournier J (February 2006). "Effects of paliroden (SR57667B) and xaliproden on adult brain neurogenesis". Current Alzheimer Research. 3 (1): 35–36. doi:10.2174/156720506775697070. PMID 16472201.
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