Xaliproden Explained

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]

Notes and References

  1. Appert-Collin A, Duong FH, Passilly Degrace P, Warter JM, Poindron P, Gies JP . 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 . 2005 . 15698508 . 10.1177/039463200501800104 . 43254260 . free .
  2. Labie C, Lafon C, Marmouget C, Saubusse P, Fournier J, Keane PE, Le Fur G, Soubrié P . 6 . 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 . May 1999 . 10369466 . 1566010 . 10.1038/sj.bjp.0702545 .
  3. Duong FH, Warter JM, Poindron P, Passilly P . Effect of the nonpeptide neurotrophic compound SR 57746A on the phenotypic survival of purified mouse motoneurons . British Journal of Pharmacology . 128 . 7 . 1385–1392 . December 1999 . 10602316 . 1571767 . 10.1038/sj.bjp.0702910 .
  4. Meininger V, Bensimon G, Bradley WR, Brooks B, Douillet P, Eisen AA, Lacomblez L, Leigh PN, Robberecht W . 6 . 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 . June 2004 . 15204012 . 10.1080/14660820410019602 . 2736180 .
  5. Lemaire L, Fournier J, Ponthus C, Le Fur Y, Confort-Gouny S, Vion-Dury J, Keane P, Cozzone PJ . 6 . Magnetic resonance imaging of the neuroprotective effect of xaliproden in rats . Investigative Radiology . 37 . 6 . 321–327 . June 2002 . 12021588 . 10.1097/00004424-200206000-00003 . 32239136 .
  6. Susman E . Xaliproden lessens oxaliplatin-mediated neuropathy . The Lancet. Oncology . 7 . 4 . 288 . April 2006 . 16598880 . 10.1016/S1470-2045(06)70639-8 .
  7. Wolf S, Barton D, Kottschade L, Grothey A, Loprinzi C . Chemotherapy-induced peripheral neuropathy: prevention and treatment strategies . European Journal of Cancer . 44 . 11 . 1507–1515 . July 2008 . 18571399 . 10.1016/j.ejca.2008.04.018 .
  8. Labie C, Canolle B, Chatelin S, Lafon C, Fournier J . Effects of paliroden (SR57667B) and xaliproden on adult brain neurogenesis . Current Alzheimer Research . 3 . 1 . 35–36 . February 2006 . 16472201 . 10.2174/156720506775697070 .

This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Xaliproden".

Except where otherwise indicated, Everything.Explained.Today is © Copyright 2009-2024, A B Cryer, All Rights Reserved. Cookie policy.