Nelotanserin Explained

Nelotanserin (former developmental code name APD-125) is a drug developed by Arena Pharmaceuticals which acts as an inverse agonist on the serotonin receptor subtype 5-HT2A and was under development for the treatment of insomnia.[1] It was shown to be effective and well tolerated in clinical trials,[2] [3] but development was halted in December 2008 because the substance did not meet the trial's effectiveness endpoints.[4] Research continues on newer analogues which may potentially be more successful.[5]

Later, nelotanserin was repurposed for the treatment of Lewy body dementia (LBD) by Axovant Sciences (now Sio Gene Therapies).[6] In late 2018, the company announced that while nelotanserin was generally well-tolerated by LBD patients in a small Phase 2 clinical trial for the treatment of REM sleep behavior disorder (RBD) and there were positive indications on some secondary trial outcomes such as sleep diaries and some polysomnogram sleep parameters, the drug failed to meet its primary endpoint of reducing the frequency of RBD episodes and would be discontinued.[7]

Notes and References

  1. Teegarden BR, Li H, Jayakumar H, Strah-Pleynet S, Dosa PI, Selaya SD, Kato N, Elwell KH, Davidson J, Cheng K, Saldana H, Frazer JM, Whelan K, Foster J, Espitia S, Webb RR, Beeley NR, Thomsen W, Morairty SR, Kilduff TS, Al-Shamma HA . 6 . Discovery of 1-[3-(4-bromo-2-methyl-2h-pyrazol-3-yl)-4-methoxyphenyl]-3-(2,4-difluorophenyl)urea (nelotanserin) and related 5-hydroxytryptamine2A inverse agonists for the treatment of insomnia . Journal of Medicinal Chemistry . 53 . 5 . 1923–36 . March 2010 . 20143782 . 10.1021/jm9007328 .
  2. Rosenberg R, Seiden DJ, Hull SG, Erman M, Schwartz H, Anderson C, Prosser W, Shanahan W, Sanchez M, Chuang E, Roth T . 6 . APD125, a selective serotonin 5-HT(2A) receptor inverse agonist, significantly improves sleep maintenance in primary insomnia . Sleep . 31 . 12 . 1663–71 . December 2008 . 19090322 . 2603489 . 10.1093/sleep/31.12.1663 .
  3. Al-Shamma HA, Anderson C, Chuang E, Luthringer R, Grottick AJ, Hauser E, Morgan M, Shanahan W, Teegarden BR, Thomsen WJ, Behan D . 6 . Nelotanserin, a novel selective human 5-hydroxytryptamine2A inverse agonist for the treatment of insomnia . The Journal of Pharmacology and Experimental Therapeutics . 332 . 1 . 281–90 . January 2010 . 19841476 . 10.1124/jpet.109.160994 . 2759858 .
  4. Web site: APD125 for Insomnia . https://web.archive.org/web/20090826062306/http://www.arenapharm.com/wt/page/apd125.html . 2009-08-26 . Arena Pharmaceuticals, Inc. .
  5. Xiong Y, Ullman B, Choi JS, Cherrier M, Strah-Pleynet S, Decaire M, Dosa PI, Feichtinger K, Teegarden BR, Frazer JM, Yoon WH, Shan Y, Whelan K, Hauser EK, Grottick AJ, Semple G, Al-Shamma H . 6 . Synthesis and in vivo evaluation of phenethylpiperazine amides: selective 5-hydroxytryptamine(2A) receptor antagonists for the treatment of insomnia . Journal of Medicinal Chemistry . 53 . 15 . 5696–706 . August 2010 . 20684606 . 10.1021/jm100479q .
  6. Web site: Nelotanserin - Axovant Gene Therapies . Adis International Ltd. . Springer Science+Business Media .
  7. Web site: Axovant Reports Results of Exploratory Phase 2 Clinical Study of Nelotanserin in Lewy Body Dementia Patients Experiencing REM Sleep Behavior Disorder . . 7 May 2023 . December 10, 2018.

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

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