NAS-181

NAS-181
Clinical data
Other names	NAS181; MCOMM
Drug class	Serotonin 5-HT1B receptor antagonist
Identifiers
	IUPAC name (2R)-2-[[3-(morpholin-4-ylmethyl)-2H-chromen-8-yl]oxymethyl]morpholine;
CAS Number	205242-61-1;
PubChem CID	9955015;
UNII	EB3GE9ZR8T;
ChEMBL	ChEMBL1789131;
Chemical and physical data
Formula	C19H26N2O4
Molar mass	346.427 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES C1CO[C@H](CN1)COC2=CC=CC3=C2OCC(=C3)CN4CCOCC4;
	InChI InChI=1S/C19H26N2O4/c1-2-16-10-15(12-21-5-8-22-9-6-21)13-25-19(16)18(3-1)24-14-17-11-20-4-7-23-17/h1-3,10,17,20H,4-9,11-14H2/t17-/m1/s1; Key:RTKDBEOSPDFLGD-QGZVFWFLSA-N;

NAS-181, also known as MCOMM, is a selective rodent serotonin 5-HT_1B receptor antagonist which is used in scientific research.^[1]^[2]

In animals, NAS-181 has been found to strongly increase acetylcholine levels in the frontal cortex and hippocampus.^[3]^[4] It has been found to block memory impairment induced by the antimuscarinic agent scopolamine and by the NMDA receptor antagonist dizocilpine (MK-801).^[5]^[6] Injection of NAS-181 directly into the nucleus accumbens has also been found to reverse the prosocial behavior induced by the serotonin releasing agent MDMA in animals.^[7]

NAS-181 was first described in the scientific literature by 1998.^[8] The drug was discovered by researchers at Astra Arcus.^[2]

References

^ Alexander SP, Christopoulos A, Davenport AP, Kelly E, Mathie A, Peters JA, et al. (December 2019). "THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: G protein-coupled receptors". British Journal of Pharmacology. 176 Suppl 1 (Suppl 1): S21–S141. doi:10.1111/bph.14748. PMC 6844580. PMID 31710717.
^ ^a ^b Slassi A (June 2002). "Recent advances in 5-HT1B/1D receptor antagonists and agonists and their potential therapeutic applications". Current Topics in Medicinal Chemistry. 2 (6): 559–574. doi:10.2174/1568026023393903. PMID 12052194.
^ Tiger M, Varnäs K, Okubo Y, Lundberg J (May 2018). "The 5-HT_1B receptor - a potential target for antidepressant treatment". Psychopharmacology. 235 (5): 1317–1334. doi:10.1007/s00213-018-4872-1 (inactive 2024-10-31). PMC 5919989. PMID 29546551.{{cite journal}}: CS1 maint: DOI inactive as of October 2024 (link)
^ Hu XJ, Wang FH, Stenfors C, Ogren SO, Kehr J (September 2007). "Effects of the 5-HT1B receptor antagonist NAS-181 on extracellular levels of acetylcholine, glutamate and GABA in the frontal cortex and ventral hippocampus of awake rats: a microdialysis study". European Neuropsychopharmacology. 17 (9): 580–586. doi:10.1016/j.euroneuro.2006.12.002. PMID 17234388.
^ Seyedabadi M, Fakhfouri G, Ramezani V, Mehr SE, Rahimian R (March 2014). "The role of serotonin in memory: interactions with neurotransmitters and downstream signaling". Experimental Brain Research. 232 (3): 723–738. doi:10.1007/s00221-013-3818-4. PMID 24430027.
^ Ruf BM, Bhagwagar Z (November 2009). "The 5-HT1B receptor: a novel target for the pathophysiology of depression". Current Drug Targets. 10 (11): 1118–1138. doi:10.2174/138945009789735192. PMID 19702551.
^ Heifets BD, Salgado JS, Taylor MD, Hoerbelt P, Cardozo Pinto DF, Steinberg EE, et al. (December 2019). "Distinct neural mechanisms for the prosocial and rewarding properties of MDMA". Science Translational Medicine. 11 (522). doi:10.1126/scitranslmed.aaw6435. PMC 7123941. PMID 31826983.
^ Berg S, Larsson LG, Rényi L, Ross SB, Thorberg SO, Thorell-Svantesson G (May 1998). "(R)-(+)-2-[[[3-(Morpholinomethyl)-2H-chromen-8-yl]oxy]methyl] morpholine methanesulfonate: a new selective rat 5-hydroxytryptamine1B receptor antagonist". Journal of Medicinal Chemistry. 41 (11): 1934–1942. doi:10.1021/jm970806i. PMID 9599242.

[AlexanderChristopoulosDavenport2019-1] Alexander SP, Christopoulos A, Davenport AP, Kelly E, Mathie A, Peters JA, et al. (December 2019). "THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: G protein-coupled receptors". British Journal of Pharmacology. 176 Suppl 1 (Suppl 1): S21–S141. doi:10.1111/bph.14748. PMC 6844580. PMID 31710717.

[Slassi2002-2] Slassi A (June 2002). "Recent advances in 5-HT1B/1D receptor antagonists and agonists and their potential therapeutic applications". Current Topics in Medicinal Chemistry. 2 (6): 559–574. doi:10.2174/1568026023393903. PMID 12052194.

[TigerVarnäsOkubo2018-3] Tiger M, Varnäs K, Okubo Y, Lundberg J (May 2018). "The 5-HT_1B receptor - a potential target for antidepressant treatment". Psychopharmacology. 235 (5): 1317–1334. doi:10.1007/s00213-018-4872-1 (inactive 2024-10-31). PMC 5919989. PMID 29546551.{{cite journal}}: CS1 maint: DOI inactive as of October 2024 (link)

[HuWangStenfors2007-4] Hu XJ, Wang FH, Stenfors C, Ogren SO, Kehr J (September 2007). "Effects of the 5-HT1B receptor antagonist NAS-181 on extracellular levels of acetylcholine, glutamate and GABA in the frontal cortex and ventral hippocampus of awake rats: a microdialysis study". European Neuropsychopharmacology. 17 (9): 580–586. doi:10.1016/j.euroneuro.2006.12.002. PMID 17234388.

[SeyedabadiFakhfouriRamezani2014-5] Seyedabadi M, Fakhfouri G, Ramezani V, Mehr SE, Rahimian R (March 2014). "The role of serotonin in memory: interactions with neurotransmitters and downstream signaling". Experimental Brain Research. 232 (3): 723–738. doi:10.1007/s00221-013-3818-4. PMID 24430027.

[RufBhagwagar2009-6] Ruf BM, Bhagwagar Z (November 2009). "The 5-HT1B receptor: a novel target for the pathophysiology of depression". Current Drug Targets. 10 (11): 1118–1138. doi:10.2174/138945009789735192. PMID 19702551.

[HeifetsSalgadoTaylor2019-7] Heifets BD, Salgado JS, Taylor MD, Hoerbelt P, Cardozo Pinto DF, Steinberg EE, et al. (December 2019). "Distinct neural mechanisms for the prosocial and rewarding properties of MDMA". Science Translational Medicine. 11 (522). doi:10.1126/scitranslmed.aaw6435. PMC 7123941. PMID 31826983.

[BergLarssonRényi1998-8] Berg S, Larsson LG, Rényi L, Ross SB, Thorberg SO, Thorell-Svantesson G (May 1998). "(R)-(+)-2-[[[3-(Morpholinomethyl)-2H-chromen-8-yl]oxy]methyl] morpholine methanesulfonate: a new selective rat 5-hydroxytryptamine1B receptor antagonist". Journal of Medicinal Chemistry. 41 (11): 1934–1942. doi:10.1021/jm970806i. PMID 9599242.

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]

NAS-181

See also

References