RS-127445

RS-127445
Clinical data
Other names	RS-127,445; MT500; MT-500
Identifiers
	IUPAC name 4-(4-fluoro-1-naphthyl)-6-isopropylpyrimidin-2-amine;
CAS Number	199864-87-4;
PubChem CID	196968;
IUPHAR/BPS	188;
ChemSpider	170590;
UNII	0JAU3P8OBM;
ChEMBL	ChEMBL473186;
CompTox Dashboard (EPA)	DTXSID60941960 ;
Chemical and physical data
Formula	C17H16FN3
Molar mass	281.334 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES Nc3nc(C(C)C)cc(n3)-c(cc2)c1ccccc1c2F;
	InChI InChI=1S/C17H16FN3/c1-10(2)15-9-16(21-17(19)20-15)13-7-8-14(18)12-6-4-3-5-11(12)13/h3-10H,1-2H3,(H2,19,20,21); Key:ZZZQXCUPAJFVBN-UHFFFAOYSA-N;
	(verify)

Chemical compound

Pharmaceutical compound

RS-127445, also known as MT-500, is a drug which acts as a potent and selective antagonist at the serotonin 5-HT_2B receptor, with around 1,000-fold selectivity over the closely related 5-HT_2A and 5-HT_2C receptors.^[1] The role of the 5-HT_2B receptor in the body is still poorly understood, and RS-127445 has been a useful tool in unravelling the function of the various systems in which this receptor is expressed.^[2]^[3]^[4] The drug was under development for potential use as a pharmaceutical drug by Roche and reached phase 1 clinical trials but was discontinued for unknown reasons.^[5]^[6]

RS-127445 has been found to diminish the head-twitch response, a behavioral proxy of psychedelic effects, induced by the psychedelic drug LSD in rats but not in mice.^[7] It also blocked the persistent antidepressant-like effects produced by LSD in rats.^[7]

References

^ Bonhaus DW, Flippin LA, Greenhouse RJ, Jaime S, Rocha C, Dawson M, et al. (July 1999). "RS-127445: a selective, high affinity, orally bioavailable 5-HT2B receptor antagonist". British Journal of Pharmacology. 127 (5): 1075–82. doi:10.1038/sj.bjp.0702632. PMC 1566110. PMID 10455251.
^ Launay JM, Hervé P, Peoc'h K, Tournois C, Callebert J, Nebigil CG, et al. (October 2002). "Function of the serotonin 5-hydroxytryptamine 2B receptor in pulmonary hypertension" (PDF). Nature Medicine. 8 (10): 1129–35. doi:10.1038/nm764. PMID 12244304. S2CID 20736218.
^ Kelly CR, Sharif NA (June 2006). "Pharmacological evidence for a functional serotonin-2B receptor in a human uterine smooth muscle cell line". The Journal of Pharmacology and Experimental Therapeutics. 317 (3): 1254–61. doi:10.1124/jpet.105.100172. PMID 16517693. S2CID 6604193.
^ Mbaki Y, Ramage AG (October 2008). "Investigation of the role of 5-HT2 receptor subtypes in the control of the bladder and the urethra in the anaesthetized female rat". British Journal of Pharmacology. 155 (3): 343–56. doi:10.1038/bjp.2008.273. PMC 2567885. PMID 18604238.
^ "Delving into the Latest Updates on MT-500 with Synapse". Synapse. 21 November 2024. Retrieved 30 November 2024.
^ Wang Q, Zhou Y, Huang J, Huang N (January 2021). "Structure, Function, and Pharmaceutical Ligands of 5-Hydroxytryptamine 2B Receptor". Pharmaceuticals (Basel). 14 (2): 76. doi:10.3390/ph14020076. PMC 7909583. PMID 33498477.
^ a b Bouloufa A, Delcourte S, Rovera R, Mouledous L, Guiard B, Haddjeri N (18 August 2025). "327. 5-HT2B Receptors Modulate the Antidepressant-like Response of the Psychedelic LSD in Rat But Not in Mice". International Journal of Neuropsychopharmacology. 28 (Supplement_2): ii117 – ii118. doi:10.1093/ijnp/pyaf052.234. ISSN 1461-1457. PMC 12359452.

This drug article relating to the nervous system is a stub. You can help Wikipedia by expanding it.

[1] Bonhaus DW, Flippin LA, Greenhouse RJ, Jaime S, Rocha C, Dawson M, et al. (July 1999). "RS-127445: a selective, high affinity, orally bioavailable 5-HT2B receptor antagonist". British Journal of Pharmacology. 127 (5): 1075–82. doi:10.1038/sj.bjp.0702632. PMC 1566110. PMID 10455251.

[2] Launay JM, Hervé P, Peoc'h K, Tournois C, Callebert J, Nebigil CG, et al. (October 2002). "Function of the serotonin 5-hydroxytryptamine 2B receptor in pulmonary hypertension" (PDF). Nature Medicine. 8 (10): 1129–35. doi:10.1038/nm764. PMID 12244304. S2CID 20736218.

[3] Kelly CR, Sharif NA (June 2006). "Pharmacological evidence for a functional serotonin-2B receptor in a human uterine smooth muscle cell line". The Journal of Pharmacology and Experimental Therapeutics. 317 (3): 1254–61. doi:10.1124/jpet.105.100172. PMID 16517693. S2CID 6604193.

[4] Mbaki Y, Ramage AG (October 2008). "Investigation of the role of 5-HT2 receptor subtypes in the control of the bladder and the urethra in the anaesthetized female rat". British Journal of Pharmacology. 155 (3): 343–56. doi:10.1038/bjp.2008.273. PMC 2567885. PMID 18604238.

[Synapse-5] "Delving into the Latest Updates on MT-500 with Synapse". Synapse. 21 November 2024. Retrieved 30 November 2024.

[WangZhouHuang2021-6] Wang Q, Zhou Y, Huang J, Huang N (January 2021). "Structure, Function, and Pharmaceutical Ligands of 5-Hydroxytryptamine 2B Receptor". Pharmaceuticals (Basel). 14 (2): 76. doi:10.3390/ph14020076. PMC 7909583. PMID 33498477.

[BouloufaDelcourteRovera2025-7] Bouloufa A, Delcourte S, Rovera R, Mouledous L, Guiard B, Haddjeri N (18 August 2025). "327. 5-HT2B Receptors Modulate the Antidepressant-like Response of the Psychedelic LSD in Rat But Not in Mice". International Journal of Neuropsychopharmacology. 28 (Supplement_2): ii117 – ii118. doi:10.1093/ijnp/pyaf052.234. ISSN 1461-1457. PMC 12359452.