Chemistry:Xaliproden

From HandWiki

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

References

  1. ↑ 1.0 1.1 1.2 1.3 "Xaliproden". 5 November 2023. https://adisinsight.springer.com/drugs/800001601. 
  2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 "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. November 2009. doi:10.1517/13543780903329089. PMID 19814656. 
  3. ↑ 3.0 3.1 3.2 "What we have learned from the Xaliproden Sanofi-aventis trials". J Nutr Health Aging 13 (4): 365–366. April 2009. doi:10.1007/s12603-009-0045-6. PMID 19300882. 
  4. ↑ "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. doi:10.1177/039463200501800104. PMID 15698508. 
  5. ↑ "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. doi:10.1080/14660820410019602. PMID 15204012. 
  6. ↑ "Magnetic resonance imaging of the neuroprotective effect of xaliproden in rats". Investigative Radiology 37 (6): 321–327. June 2002. doi:10.1097/00004424-200206000-00003. PMID 12021588. 
  7. ↑ "Biochemical and electrophysiological properties of SR 57746A, a new, potent 5-HT1A receptor agonist". Fundam Clin Pharmacol 7 (9): 487–497. 1993. doi:10.1111/j.1472-8206.1993.tb00253.x. PMID 8314196. 
  8. ↑ 8.0 8.1 "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. February 1994. doi:10.1016/0014-2999(94)90768-4. PMID 8013540. 
  9. ↑ "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. doi:10.1038/sj.bjp.0702545. PMID 10369466. 
  10. ↑ "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. doi:10.1038/sj.bjp.0702910. PMID 10602316. 
  11. ↑ "Neuropsychopharmacological profile in rodents of SR 57746A, a new, potent 5-HT1A receptor agonist". Fundam Clin Pharmacol 7 (8): 413–427. 1993. PMID 7904976. 
  12. ↑ "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. September 2009. doi:10.1111/j.1476-5381.2009.00249.x. PMID 19508400. 
  13. ↑ "Paliroden". 2 October 2007. https://adisinsight.springer.com/drugs/800013042. 
  14. ↑ "Effects of paliroden (SR57667B) and xaliproden on adult brain neurogenesis". Current Alzheimer Research 3 (1): 35–36. February 2006. doi:10.2174/156720506775697070. PMID 16472201. 



Retrieved from "https://handwiki.org/wiki/index.php?title=Chemistry:Xaliproden&oldid=4583778"