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]
References
^Teegarden BR, Li H, Jayakumar H, Strah-Pleynet S, Dosa PI, Selaya SD, et al. (March 2010). "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.
doi:
10.1021/jm9007328.
PMID20143782.
^Al-Shamma HA, Anderson C, Chuang E, Luthringer R, Grottick AJ, Hauser E, et al. (January 2010). "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.
doi:
10.1124/jpet.109.160994.
PMID19841476.
S2CID2759858.
^Xiong Y, Ullman B, Choi JS, Cherrier M, Strah-Pleynet S, Decaire M, et al. (August 2010). "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.
doi:
10.1021/jm100479q.
PMID20684606.
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]
References
^Teegarden BR, Li H, Jayakumar H, Strah-Pleynet S, Dosa PI, Selaya SD, et al. (March 2010). "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.
doi:
10.1021/jm9007328.
PMID20143782.
^Al-Shamma HA, Anderson C, Chuang E, Luthringer R, Grottick AJ, Hauser E, et al. (January 2010). "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.
doi:
10.1124/jpet.109.160994.
PMID19841476.
S2CID2759858.
^Xiong Y, Ullman B, Choi JS, Cherrier M, Strah-Pleynet S, Decaire M, et al. (August 2010). "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.
doi:
10.1021/jm100479q.
PMID20684606.