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Xaliproden

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

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 peripheral neuropathy associated with chemotherapy. see wikepedia.com.

Xaliproden, is an orally-active, synthetic, non-peptidic 5-hydroxytryptamine (5-HT) 1A receptor agonist with neurotrophic and neuroprotective activities. Although its mechanism of action is not fully understood, xaliproden appears to either mimic the effects of neurotrophins or stimulate their synthesis, thereby stimulating neuronal cell differentiation and proliferation and inhibiting neuronal cell death. The neuroprotective effect of this agent involves the activation of MAP kinase pathways via stimulation of the 5-HT1A receptor. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus).

Current developer:   Sanofi-Aventis Inc 

 1: Porzner M, Müller T, Seufferlein T. SR 57746A/xaliproden, a non-peptide neurotrophic compound: prospects and constraints for the treatment of nervous system diseases. Expert Opin Investig Drugs. 2009 Nov;18(11):1765-72. Review. PubMed PMID: 19814656.

2: Sabbagh MN. Drug development for Alzheimer's disease: where are we now and where are we headed? Am J Geriatr Pharmacother. 2009 Jun;7(3):167-85. Review. PubMed PMID: 19616185.

3: Martel JC, Assié MB, Bardin L, Depoortère R, Cussac D, Newman-Tancredi A. 5-HT1A receptors are involved in the effects of xaliproden on G-protein activation, neurotransmitter release and nociception. Br J Pharmacol. 2009 Sep;158(1):232-42. Epub 2009 Jun 5. PubMed PMID: 19508400; PubMed Central PMCID: PMC2795245.

4: Gordon PH, Corcia P, Lacomblez L, Pochigaeva K, Abitbol JL, Cudkowicz M, Leigh PN, Meininger V. Defining survival as an outcome measure in amyotrophic lateral sclerosis. Arch Neurol. 2009 Jun;66(6):758-61. PubMed PMID: 19506136.

5: Douillet P, Orgogozo JM. What we have learned from the Xaliproden Sanofi-aventis trials. J Nutr Health Aging. 2009 Apr;13(4):365-6. PubMed PMID: 19300882.

6: Chang CW, Poteet E, Schetz JA, Gümüş ZH, Weinstein H. Towards a quantitative representation of the cell signaling mechanisms of hallucinogens: measurement and mathematical modeling of 5-HT1A and 5-HT2A receptor-mediated ERK1/2 activation. Neuropharmacology. 2009;56 Suppl 1:213-25. Epub 2008 Aug 13. PubMed PMID: 18762202; PubMed Central PMCID: PMC2635340.

7: Wolf S, Barton D, Kottschade L, Grothey A, Loprinzi C. Chemotherapy-induced peripheral neuropathy: prevention and treatment strategies. Eur J Cancer. 2008 Jul;44(11):1507-15. Epub 2008 Jun 18. Review. PubMed PMID: 18571399.

8: Wilkes G. Peripheral neuropathy related to chemotherapy. Semin Oncol Nurs. 2007 Aug;23(3):162-73. Review. PubMed PMID: 17693343.

9: Bayes M, Rabasseda X, Prous JR. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2006 Nov;28(9):657-78. PubMed PMID: 17200730.

10: Gibson TB, Ranganathan A, D'Orazio A; American Society of Clinical Oncology. Highlights From: the 2006 American Society of Clinical Oncology Gastrointestinal Cancers Symposium San Francisco, CA, January 2006. Clin Colorectal Cancer. 2006 Mar;5(6):398-402. PubMed PMID: 16635277.

11: Susman E. Xaliproden lessens oxaliplatin-mediated neuropathy. Lancet Oncol. 2006 Apr;7(4):288. PubMed PMID: 16598880.

12: Labie C, Canolle B, Chatelin S, Lafon C, Fournier J. Effects of paliroden (SR57667B) and xaliproden on adult brain neurogenesis. Curr Alzheimer Res. 2006 Feb;3(1):35-6. Review. PubMed PMID: 16472201.

13: Doraiswamy PM, Xiong GL. Pharmacological strategies for the prevention of Alzheimer's disease. Expert Opin Pharmacother. 2006 Jan;7(1):1-10. Review. PubMed PMID: 16370917.

14: Appert-Collin A, Duong FH, Passilly DeGrace P, Bennasroune A, Poindron P, Warter JM, Gies JP. Xaliproden (SR57746A) induces 5-HT1A receptor-mediated MAP kinase activation in PC12 cells. Int J Immunopathol Pharmacol. 2005 Apr-Jun;18(2):233-44. PubMed PMID: 15888246.

15: 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. Int J Immunopathol Pharmacol. 2005 Jan-Mar;18(1):21-31. PubMed PMID: 15698508.

16: Meininger V, Bensimon G, Bradley WR, Brooks B, Douillet P, Eisen AA, Lacomblez L, Leigh PN, Robberecht W. Efficacy and safety of xaliproden in amyotrophic lateral sclerosis: results of two phase III trials. Amyotroph Lateral Scler Other Motor Neuron Disord. 2004 Jun;5(2):107-17. PubMed PMID: 15204012.

17: Lacomblez L, Bensimon G, Douillet P, Doppler V, Salachas F, Meininger V. Xaliproden in amyotrophic lateral sclerosis: early clinical trials. Amyotroph Lateral Scler Other Motor Neuron Disord. 2004 Jun;5(2):99-106. PubMed PMID: 15204011.

18: Appert-Collin A, Duong FH, Passilly-Degrace P, Gies JP, Warter JM, Poindron P. Quantification of neurotrophin mRNA expression in PMN mouse: modulation by xaliproden. Int J Immunopathol Pharmacol. 2004 May-Aug;17(2):157-64. PubMed PMID: 15171816.

19: Xaliproden: SR 57746, SR 57746A, xaliproden hydrochloride, xaliprodene. Drugs R D. 2003;4(6):386-8. Review. PubMed PMID: 14584974.

20: Lemaire L, Fournier J, Ponthus C, Le Fur Y, Confort-Gouny S, Vion-Dury J, Keane P, Cozzone PJ. Magnetic resonance imaging of the neuroprotective effect of xaliproden in rats. Invest Radiol. 2002 Jun;37(6):321-7. PubMed PMID: 12021588.

21: Moriwaka F, Tashiro K. [The advance in the research and therapeutic trials of amyotrophic lateral sclerosis]. Rinsho Shinkeigaku. 2000 Dec;40(12):1258-60. Review. Japanese. PubMed PMID: 11464472.

22: Hurko O, Walsh FS. Novel drug development for amyotrophic lateral sclerosis. J Neurol Sci. 2000 Nov 1;180(1-2):21-8. Review. PubMed PMID: 11090860.

23: Duong FH, Warter JM, Poindron P, Passilly P. Effect of the nonpeptide neurotrophic compound SR 57746A on the phenotypic survival of purified mouse motoneurons. Br J Pharmacol. 1999 Dec;128(7):1385-92. PubMed PMID: 10602316; PubMed Central PMCID: PMC1571767.

24: Bourrié B, Bribes E, Esclangon M, Garcia L, Marchand J, Thomas C, Maffrand JP, Casellas P. The neuroprotective agent SR 57746A abrogates experimental autoimmune encephalomyelitis and impairs associated blood-brain barrier disruption: implications for multiple sclerosis treatment. Proc Natl Acad Sci U S A. 1999 Oct 26;96(22):12855-9. PubMed PMID: 10536012; PubMed Central PMCID: PMC23131.

25: Labie C, Lafon C, Marmouget C, Saubusse P, Fournier J, Keane PE, Le Fur G, Soubrié P. Effect of the neuroprotective compound SR57746A on nerve growth factor synthesis in cultured astrocytes from neonatal rat cortex. Br J Pharmacol. 1999 May;127(1):139-44. PubMed PMID: 10369466; PubMed Central PMCID: PMC1566010.

26: Iwasaki Y, Shiojima T, Kinoshita M, Ikeda K. SR57746A: a survival factor for motor neurons in vivo. J Neurol Sci. 1998 Oct;160 Suppl 1:S92-6. PubMed PMID: 9851657.

27: Duong F, Fournier J, Keane PE, Guénet JL, Soubrié P, Warter JM, Borg J, Poindron P. The effect of the nonpeptide neurotrophic compound SR 57746A on the progression of the disease state of the pmn mouse. Br J Pharmacol. 1998 Jun;124(4):811-7. PubMed PMID: 9690875; PubMed Central PMCID: PMC1565442.

28: Fournier J, Boutot G, Keane PE, Maffrand JP, Le Fur G, Soubrié P. The non-peptide neuroprotective agents SR 57746A interacts with neurotrophin 3 to induce differentiation in the PC12 cell-line. J Pharm Pharmacol. 1998 Mar;50(3):323-7. PubMed PMID: 9600726.

29: Magazin M, Schiltz P, Zachayus JL, Cavrois E, Caput D, Ferrara P. Inhibition of lysophosphatidic acid-induced neurite retraction and cell rounding by SR 57746A. Brain Res Mol Brain Res. 1998 Jan;53(1-2):301-6. PubMed PMID: 9473704.

30: Terranova JP, Kan JP, Storme JJ, Perreaut P, Le Fur G, Soubrié P. Administration of amyloid beta-peptides in the rat medial septum causes memory deficits: reversal by SR 57746A, a non-peptide neurotrophic compound. Neurosci Lett. 1996 Aug 2;213(2):79-82. PubMed PMID: 8858613.

31: Ruigt GS, Makkink WK, Konings PN. SR 57746A attenuates cytostatic drug-induced reduction of neurite outgrowth in co-cultures of rat dorsal root ganglia and Schwann cells. Neurosci Lett. 1996 Jan 12;203(1):9-12. PubMed PMID: 8742034.

32: Pradines A, Magazin M, Schiltz P, Le Fur G, Caput D, Ferrara P. Evidence for nerve growth factor-potentiating activities of the nonpeptidic compound SR 57746A in PC12 cells. J Neurochem. 1995 May;64(5):1954-64. PubMed PMID: 7722483.

33: Croci T, Landi M, Bianchetti A, Manara L. Drug-induced defaecation in rats: role of central 5-HT1A receptors. Br J Pharmacol. 1995 May;115(1):203-9. PubMed PMID: 7647978; PubMed Central PMCID: PMC1908762.

34: Cervo L, Bendotti C, Tarizzo G, Cagnotto A, Skorupska M, Mennini T, Samanin R. Potential antidepressant properties of SR 57746A, a novel compound with selectivity and high affinity for 5-HT1A receptors. Eur J Pharmacol. 1994 Feb 21;253(1-2):139-47. PubMed PMID: 8013540.

35: Fessler B. [Alzheimer's disease: irreparable damage in the brain?]. Med Monatsschr Pharm. 1993 Nov;16(11):334-5. German. PubMed PMID: 8272002.

36: Fournier J, Steinberg R, Gauthier T, Keane PE, Guzzi U, Coudé FX, Bougault I, Maffrand JP, Soubrié P, Le Fur G. Protective effects of SR 57746A in central and peripheral models of neurodegenerative disorders in rodents and primates. Neuroscience. 1993 Aug;55(3):629-41. PubMed PMID: 8413926.

37: Bachy A, Steinberg R, Santucci V, Fournier M, Landi M, Hamon M, Manara L, Keane PE, Soubrié P, Le Fur G. Biochemical and electrophysiological properties of SR 57746A, a new, potent 5-HT1A receptor agonist. Fundam Clin Pharmacol. 1993;7(9):487-97. PubMed PMID: 8314196.

38: Simiand J, Keane PE, Barnouin MC, Keane M, Soubrié P, Le Fur G. Neuropsychopharmacological profile in rodents of SR 57746A, a new, potent 5-HT1A receptor agonist. Fundam Clin Pharmacol. 1993;7(8):413-27. PubMed PMID: 7904976.