Xaliproden
Chemical compound
From Wikipedia, the free encyclopedia
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]
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| Trade names | Xaprila (former tentative) |
| Other names | Xaliprodene; SR-57746; SR57746; SR-57,746; SR-57746A; SR57746A |
| Routes of administration | Oral[1] |
| Drug class | Serotonin 5-HT1A receptor agonist |
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| Formula | C24H22F3N |
| Molar mass | 381.442 g·mol−1 |
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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]