{{cs1 config|name-list-style=vanc|display-authors=6}} {{Infobox drug | drug_name = | image = AZD-3783.svg | image_class = skin-invert-image | width = | caption =
<!-- Clinical data --> | pronounce = | tradename = | Drugs.com = | MedlinePlus = | licence_CA = | licence_EU = | DailyMedID = | licence_US = | pregnancy_AU = | pregnancy_category = | dependency_liability = | addiction_liability = | routes_of_administration = Unspecified<ref name="AdisInsight" /> | class = Serotonin 5-HT<sub>1B</sub> receptor antagonist | ATC_prefix = | ATC_suffix =
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<!-- Pharmacokinetic data --> | bioavailability = | protein_bound = | metabolism = | metabolites = | onset = | elimination_half-life = | duration_of_action = | excretion =
<!-- Identifiers --> | CAS_number = 1162658-64-1 | CAS_supplemental = | PubChem = 25067561 | IUPHAR_ligand = | DrugBank = | ChemSpiderID = 24651803 | UNII = 3NC9ASE900 | KEGG = | ChEBI = | ChEMBL = 602875 | NIAID_ChemDB = | PDB_ligand = | synonyms = AZD3783; AZ-12320927; AZ12320927
<!-- Chemical data --> | IUPAC_name = (2''R'')-6-methoxy-8-(4-methylpiperazin-1-yl)-''N''-(4-morpholin-4-ylphenyl)-3,4-dihydro-2''H''-chromene-2-carboxamide | C=26 | H=34 | N=4 | O=4 | SMILES = CN1CCN(CC1)C2=CC(=CC3=C2O[C@H](CC3)C(=O)NC4=CC=C(C=C4)N5CCOCC5)OC | StdInChI = 1S/C26H34N4O4/c1-28-9-11-30(12-10-28)23-18-22(32-2)17-19-3-8-24(34-25(19)23)26(31)27-20-4-6-21(7-5-20)29-13-15-33-16-14-29/h4-7,17-18,24H,3,8-16H2,1-2H3,(H,27,31)/t24-/m1/s1 | StdInChIKey = SKOWCFJEXPLGNE-XMMPIXPASA-N }}
'''AZD-3783''' is a serotonin 5-HT<sub>1B</sub> receptor antagonist which was under development for the treatment of major depressive disorder and anxiety disorders.<ref name="AdisInsight">{{cite web | title=AZD 3783 | website=AdisInsight | date=18 December 2007 | url=https://adisinsight.springer.com/drugs/800025787 | access-date=28 February 2025}}</ref><ref name="Synapse">{{cite web | title=Delving into the Latest Updates on AZD-3783 with Synapse | website=Synapse | date=23 January 2025 | url=https://synapse.patsnap.com/drug/f9a1583574a94460a265e2edd343d1c5 | access-date=28 February 2025}}</ref><ref name="TigerVarnäsOkubo2018">{{cite journal | vauthors = Tiger M, Varnäs K, Okubo Y, Lundberg J | title = The 5-HT<sub>1B</sub> 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 | quote = Given the inhibitory effect of 5-HT1B receptors on serotonin release and the predominantly prevailing serotonin hypothesis of MDD, it makes sense to block 5-HT1B receptors for antidepressant effect (Slassi 2002). Thus far, most 5-HT1B receptor drug candidates for MDD treatment have been antagonists, such as SB-616234-A (Dawson et al. 2006), AZD3783 (Zhang et al. 2011), and AR-A000002 (Hudzik et al. 2003). It has been proposed that 5-HT1 receptor activation counteracts the serotonin-enhancing effects of SSRI and thereby contribute to the latency of therapeutic effect (Blier and de Montigny 1994; Nutt 2002). SSRI-induced downregulation of 5-HT1 receptors would then restore the serotonin-elevating effects of the drugs and hence enable a clinical effect, providing a rationale for blocking 5-HT1B receptors for rapid antidepressant response. }}</ref><ref name="ZhangZhouWang2011">{{cite journal | vauthors = Zhang M, Zhou D, Wang Y, Maier DL, Widzowski DV, Sobotka-Briner CD, Brockel BJ, Potts WM, Shenvi AB, Bernstein PR, Pierson ME | display-authors = 6 | title = Preclinical pharmacology and pharmacokinetics of AZD3783, a selective 5-hydroxytryptamine 1B receptor antagonist | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 339 | issue = 2 | pages = 567–578 | date = November 2011 | pmid = 21825000 | doi = 10.1124/jpet.110.174433 }}</ref><ref name="VarnäsNybergKarlsson2011">{{cite journal | vauthors = Varnäs K, Nyberg S, Karlsson P, Pierson ME, Kågedal M, Cselényi Z, McCarthy D, Xiao A, Zhang M, Halldin C, Farde L | display-authors = 6 | title = Dose-dependent binding of AZD3783 to brain 5-HT1B receptors in non-human primates and human subjects: a positron emission tomography study with [11C]AZ10419369 | journal = Psychopharmacology | volume = 213 | issue = 2–3 | pages = 533–545 | date = February 2011 | pmid = 21234549 | doi = 10.1007/s00213-011-2165-z }}</ref> It was being developed by AstraZeneca.<ref name="AdisInsight" /><ref name="Synapse" /> The drug reached phase 1 clinical trials prior to the discontinuation of its development.<ref name="AdisInsight" /><ref name="Synapse" /> It was discontinued following unexpected neurotoxicity findings in animals.<ref name="ChangCiaccioSchroeder2014">{{cite journal | vauthors = Chang JC, Ciaccio P, Schroeder P, Wright L, Westwood R, Berg AL | title = Pathology and Neurotoxicity in Dogs after Repeat Dose Exposure to a Serotonin 5-HT1B Inhibitor | journal = Journal of Toxicologic Pathology | volume = 27 | issue = 1 | pages = 31–42 | date = April 2014 | pmid = 24791065 | pmc = 4000071 | doi = 10.1293/tox.2013-0033 }}</ref>
== See also == * AZD-1134 * List of investigational antidepressants * List of investigational anxiolytics
== References == {{Reflist}}
{{Serotonin receptor modulators}}
Category:5-HT1B antagonists Category:Abandoned drugs Category:Benzopyrans Category:Carboxamides Category:Drugs developed by AstraZeneca Category:Experimental antidepressants Category:Experimental anxiolytics Category:Methoxy compounds Category:4-Morpholinyl compounds Category:Neurotoxins Category:4-Aminophenyl compounds Category:4-Methylpiperazin-1-yl compounds
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