NAS-181

{{Short description|Serotonin 5-HT1B receptor antagonist}}

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| class = Serotonin 5-HT_1B receptor antagonist

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| CAS_number = 205242-61-1

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| PubChem = 9955015

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| UNII = EB3GE9ZR8T

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| ChEMBL = 1789131

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| synonyms = NAS181; MCOMM

| IUPAC_name = (2R)-2-[[3-(morpholin-4-ylmethyl)-2H-chromen-8-yl]oxymethyl]morpholine

| C=19 | H=26 | N=2 | O=4

| SMILES = C1CO[C@H](CN1)COC2=CC=CC3=C2OCC(=C3)CN4CCOCC4

| StdInChI = 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

| StdInChIKey = RTKDBEOSPDFLGD-QGZVFWFLSA-N

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NAS-181, also known as MCOMM, is a selective rodent serotonin 5-HT_1B receptor antagonist which is used in scientific research.{{cite journal | vauthors = Alexander SP, Christopoulos A, Davenport AP, Kelly E, Mathie A, Peters JA, Veale EL, Armstrong JF, Faccenda E, Harding SD, Pawson AJ, Sharman JL, Southan C, Davies JA | title = THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: G protein-coupled receptors | journal = British Journal of Pharmacology | volume = 176 Suppl 1 | issue = Suppl 1 | pages = S21–S141 | date = December 2019 | pmid = 31710717 | pmc = 6844580 | doi = 10.1111/bph.14748 }}

In animals, NAS-181 has been found to strongly increase acetylcholine levels in the frontal cortex and hippocampus.{{cite journal | vauthors = Tiger M, Varnäs K, Okubo Y, Lundberg J | title = The 5-HT_1B receptor - a potential target for antidepressant treatment | journal = Psychopharmacology | volume = 235 | issue = 5 | pages = 1317–1334 | date = May 2018 | pmid = 29546551 | pmc = 5919989 | doi = 10.1007/s00213-018-4872-1 }}{{cite journal | vauthors = Hu XJ, Wang FH, Stenfors C, Ogren SO, Kehr J | title = 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 | journal = European Neuropsychopharmacology | volume = 17 | issue = 9 | pages = 580–586 | date = September 2007 | pmid = 17234388 | doi = 10.1016/j.euroneuro.2006.12.002 }} It has been found to block memory impairment induced by the antimuscarinic agent scopolamine and by the NMDA receptor antagonist dizocilpine (MK-801).{{cite journal | vauthors = Seyedabadi M, Fakhfouri G, Ramezani V, Mehr SE, Rahimian R | title = The role of serotonin in memory: interactions with neurotransmitters and downstream signaling | journal = Experimental Brain Research | volume = 232 | issue = 3 | pages = 723–738 | date = March 2014 | pmid = 24430027 | doi = 10.1007/s00221-013-3818-4 }}{{cite journal | vauthors = Ruf BM, Bhagwagar Z | title = The 5-HT1B receptor: a novel target for the pathophysiology of depression | journal = Current Drug Targets | volume = 10 | issue = 11 | pages = 1118–1138 | date = November 2009 | pmid = 19702551 | doi = 10.2174/138945009789735192 }} 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.{{cite journal | vauthors = Heifets BD, Salgado JS, Taylor MD, Hoerbelt P, Cardozo Pinto DF, Steinberg EE, Walsh JJ, Sze JY, Malenka RC | title = Distinct neural mechanisms for the prosocial and rewarding properties of MDMA | journal = Science Translational Medicine | volume = 11 | issue = 522 | date = December 2019 | pmid = 31826983 | pmc = 7123941 | doi = 10.1126/scitranslmed.aaw6435 }}

NAS-181 was first described in the scientific literature by 1998.{{cite journal | vauthors = Berg S, Larsson LG, Rényi L, Ross SB, Thorberg SO, Thorell-Svantesson G | title = (R)-(+)-2-[[[3-(Morpholinomethyl)-2H-chromen-8-yl]oxy]methyl] morpholine methanesulfonate: a new selective rat 5-hydroxytryptamine1B receptor antagonist | journal = Journal of Medicinal Chemistry | volume = 41 | issue = 11 | pages = 1934–1942 | date = May 1998 | pmid = 9599242 | doi = 10.1021/jm970806i }} The drug was discovered by researchers at Astra Arcus.{{cite journal | vauthors = Slassi A | title = Recent advances in 5-HT1B/1D receptor antagonists and agonists and their potential therapeutic applications | journal = Current Topics in Medicinal Chemistry | volume = 2 | issue = 6 | pages = 559–574 | date = June 2002 | pmid = 12052194 | doi = 10.2174/1568026023393903 }}