{{cs1 config|name-list-style=vanc|display-authors=6}} {{Infobox drug | drug_name = | image = AZD-1134.png | 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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<!-- Identifiers --> | CAS_number = 442548-99-4 | CAS_supplemental = | PubChem = 9830790 | PubChemSubstance = | IUPHAR_ligand = | DrugBank = | ChemSpiderID = 8006524 | UNII = GR7FP8T3TF | KEGG = | ChEBI = | ChEMBL = 602674 | NIAID_ChemDB = | PDB_ligand = | synonyms =
<!-- Chemical data --> | IUPAC_name = 6-fluoro-8-(4-methylpiperazin-1-yl)-4-oxo-''N''-[4-(4-propanoylpiperazin-1-yl)phenyl]chromene-2-carboxamide | C=28 | H=32 | F=1 | N=5 | O=4 | SMILES = CCC(=O)N1CCN(CC1)C2=CC=C(C=C2)NC(=O)C3=CC(=O)C4=C(O3)C(=CC(=C4)F)N5CCN(CC5)C | StdInChI = 1S/C28H32FN5O4/c1-3-26(36)34-14-12-32(13-15-34)21-6-4-20(5-7-21)30-28(37)25-18-24(35)22-16-19(29)17-23(27(22)38-25)33-10-8-31(2)9-11-33/h4-7,16-18H,3,8-15H2,1-2H3,(H,30,37) | StdInChIKey = CKBARMWSFIJZTL-UHFFFAOYSA-N }}
'''AZD-1134''' is an investigational new drug that was being evaluated for the treatment of major depressive disorder and anxiety disorders but was never marketed.<ref name="AdisInsight">{{cite web | title=AZD 1134 | website=AdisInsight | date=31 March 2004 | url=https://adisinsight.springer.com/drugs/800017898 | access-date=11 December 2024}}</ref><ref name="HudzikSmolkaLitwin2003">{{cite journal | vauthors = Hudzik T, Smolka J, Litwin L, Porrey T, Pierson E | title=P.1.016 In vivo pharmacology of AZD1134, a novel 5-HT1B antagonist | journal=European Neuropsychopharmacology | volume=13 | date=2003 | doi=10.1016/S0924-977X(03)91727-5 | pages=S181–S182}}</ref><ref name="SmaginSongCross2003">{{cite journal | vauthors = Smagin GN, Song D, Cross AJ, Mrzljak | title=P.1.094 AZD1134, a high affinity 5-HT1B receptor antagonist activates serotonin turnover and release in guinea pig brain | journal=European Neuropsychopharmacology | volume=13 | date=2003 | doi=10.1016/S0924-977X(03)91804-9 | page=S214}}</ref><ref name="MaierSobotka-BrinerDing2009">{{cite journal | vauthors = Maier DL, Sobotka-Briner C, Ding M, Powell ME, Jiang Q, Hill G, Heys JR, Elmore CS, Pierson ME, Mrzljak L | title = [N-methyl-3H3]AZ10419369 binding to the 5-HT1B receptor: in vitro characterization and in vivo receptor occupancy | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 330 | issue = 1 | pages = 342–351 | date = July 2009 | pmid = 19401496 | doi = 10.1124/jpet.109.150722 }}</ref>
== Pharmacology == AZD-1134 is a selective serotonin 5-HT<sub>1B</sub> receptor antagonist. It has been found to increase serotonin levels in the dorsal hippocampus in animals and to increase serotonin turnover (as measured by 5-HIAA/serotonin ratio) in the cerebral cortex, hypothalamus, hippocampus, and striatum.<ref name="SmaginSongCross2003" /> Alone, AZD-1134 increased hippocampal serotonin levels to 179% of baseline, and in combination with the selective serotonin reuptake inhibitor (SSRI) citalopram, it increased levels to 950% of baseline.<ref name="SmaginSongCross2003" /> The increases in serotonin levels and turnover with AZD-1134 are presumably due to blockade of inhibitory presynaptic 5-HT<sub>1B</sub> autoreceptors.<ref name="SmaginSongCross2003" /> AZD-1134 administered alone produced antidepressant-like effects in animals.<ref name="HudzikSmolkaLitwin2003" />
== History == AZD-1134 reached preclinical research prior to the discontinuation of its development.<ref name="AdisInsight" /> It was under development by AstraZeneca.<ref name="AdisInsight" /> Another selective serotonin 5-HT<sub>1B</sub> receptor antagonist, AZD-3783, was also subsequently developed and studied by AstraZeneca.<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 | title = Preclinical pharmacology and pharmacokinetics of AZD3783, a selective 5-hydroxytryptamine 1B receptor antagonist | journal = J Pharmacol Exp Ther | volume = 339 | issue = 2 | pages = 567–578 | date = November 2011 | pmid = 21825000 | doi = 10.1124/jpet.110.174433 | url = }}</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 | 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 (Berl) | volume = 213 | issue = 2–3 | pages = 533–545 | date = February 2011 | pmid = 21234549 | doi = 10.1007/s00213-011-2165-z | url = }}</ref> However, this drug was later found to produce unexpected neurotoxicity.<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 = J Toxicol Pathol | volume = 27 | issue = 1 | pages = 31–42 | date = April 2014 | pmid = 24791065 | pmc = 4000071 | doi = 10.1293/tox.2013-0033 | url = }}</ref>
==References== {{Reflist}}
{{Serotonin receptor modulators}}
Category:5-HT1B antagonists Category:Abandoned drugs Category:Carboxamides Category:Drugs developed by AstraZeneca Category:Experimental antidepressants Category:Experimental anxiolytics Category:Fluoroarenes Category:Chromones Category:Piperazines Category:Acetamides