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Xaliproden

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Xaliproden
Clinical data
Trade namesXaprila (former tentative)
Other namesXaliprodene; SR-57746; SR57746; SR-57,746; SR-57746A; SR57746A
Routes of
administration		Oral[1]
Drug classSerotonin 5-HT1A receptor agonist
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 X markN
  • Key:WJJYZXPHLSLMGE-UHFFFAOYSA-N X markN
 X markNcheckY (what is this?)  (verify)

Xaliproden (developmental code names SR-57746 and SR-57746A) is a serotonin 5-HT1A receptor agonist which was under development for the treatment of Alzheimer's disease, amyotrophic lateral sclerosis (ALS), cancer pain, and multiple sclerosis but was never marketed.[1][2][3][4][5][6] It is taken orally.[1]

The drug acts as a selective and potent full agonist of the serotonin 5-HT1A receptor.[2][7][8] However, it also shows much lower affinity for sigma receptors.[2] Xaliproden produces neurotrophic and neuroprotective effects in preclinical research.[2][9][10] It also fully substitutes for the serotonin 5-HT1A receptor full agonist 8-OH-DPAT in rodent drug discrimination tests and produces antidepressant-like, anxiolytic-like, antiaggressive, and analgesic effects in rodents.[2][11][8][12] The drug efficiently crosses the blood–brain barrier in rodents.[2]

Side effects of xaliproden in humans include diarrhea, nausea, vomiting, insomnia, dizziness, vertigo, asthenia or fatigue, paresthesia, tinnitus, and anxiety.[2]

Development of xaliproden for Alzheimer's disease and ALS was discontinued in 2007 following analysis of Phase III data.[1] In addition development for cancer pain was discontinued in 2009.[1] The drug showed an effect on hippocampal volume that suggested slowing of atrophy in clinical trials of people with Alzheimer's disease.[3] However, there was insufficient clinical evidence for effectiveness in counteracting Alzheimer's disease-related cognitive decline.[3] Similarly, while there were some indicators of effectiveness 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.

Paliroden (SR-57667; SR-57667B), an analogue of xaliproden, was also investigated for treatment of Alzheimer's disease and Parkinson's disease, and reached phase 2 trials for these indications, but development was likewise discontinued.[13][14]

See also

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References

[edit]
  1. 1 2 3 4 5 "Xaliproden". AdisInsight. 5 November 2023. Retrieved 28 July 2026.
  2. 1 2 3 4 5 6 7 Porzner M, Müller T, Seufferlein T (November 2009). "SR 57746A/xaliproden, a non-peptide neurotrophic compound: prospects and constraints for the treatment of nervous system diseases". Expert Opin Investig Drugs. 18 (11): 1765–1772. doi:10.1517/13543780903329089. PMID 19814656.
  3. 1 2 3 Douillet P, Orgogozo JM (April 2009). "What we have learned from the Xaliproden Sanofi-aventis trials". J Nutr Health Aging. 13 (4): 365–366. doi:10.1007/s12603-009-0045-6. PMC 12877523. PMID 19300882.
  4. ↑ 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.
  5. ↑ 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.
  6. ↑ 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.
  7. ↑ Bachy A, Steinberg R, Santucci V, Fournier M, Landi M, Hamon M, Manara L, Keane PE, Soubrié P, Le Fur G (1993). "Biochemical and electrophysiological properties of SR 57746A, a new, potent 5-HT1A receptor agonist". Fundam Clin Pharmacol. 7 (9): 487–497. doi:10.1111/j.1472-8206.1993.tb00253.x. PMID 8314196.
  8. 1 2 Cervo L, Bendotti C, Tarizzo G, Cagnotto A, Skorupska M, Mennini T, Samanin R (February 1994). "Potential antidepressant properties of SR 57746A, a novel compound with selectivity and high affinity for 5-HT1A receptors". Eur J Pharmacol. 253 (1–2): 139–147. doi:10.1016/0014-2999(94)90768-4. PMID 8013540.
  9. ↑ 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.
  10. ↑ 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.
  11. ↑ Simiand J, Keane PE, Barnouin MC, Keane M, Soubrié P, Le Fur G (1993). "Neuropsychopharmacological profile in rodents of SR 57746A, a new, potent 5-HT1A receptor agonist". Fundam Clin Pharmacol. 7 (8): 413–427. PMID 7904976.
  12. ↑ Martel JC, Assié MB, Bardin L, Depoortère R, Cussac D, Newman-Tancredi A (September 2009). "5-HT1A receptors are involved in the effects of xaliproden on G-protein activation, neurotransmitter release and nociception". Br J Pharmacol. 158 (1): 232–242. doi:10.1111/j.1476-5381.2009.00249.x. PMC 2795245. PMID 19508400.
  13. ↑ "Paliroden". AdisInsight. 2 October 2007. Retrieved 28 July 2026.
  14. ↑ 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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