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Revision as of 10:13, 11 December 2024 editAlyInWikiWonderland (talk | contribs)Autopatrolled, Extended confirmed users81,666 edits ←Created page with '{{Infobox drug | drug_name = | 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 receptor anta...'  Revision as of 12:37, 11 December 2024 edit undoDMacks (talk | contribs)Edit filter managers, Autopatrolled, Administrators186,266 edits +imageNext edit →
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Revision as of 12:37, 11 December 2024

Pharmaceutical compound
AZD-1134
Clinical data
Routes of
administration		Unspecified
Drug classSerotonin 5-HT1B receptor antagonist
Identifiers
IUPAC name
  • 6-fluoro-8-(4-methylpiperazin-1-yl)-4-oxo-N-chromene-2-carboxamide
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
Chemical and physical data
FormulaC28H32FN5O4
Molar mass521.593 g·mol
3D model (JSmol)
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
InChI
  • InChI=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)
  • Key:CKBARMWSFIJZTL-UHFFFAOYSA-N

AZD-1134 is a selective serotonin 5-HT1B receptor antagonist which was under development for the treatment major depressive disorder and anxiety disorders but was never marketed. Its route was unspecified.

The drug 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. 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. The increases in serotonin levels and turnover with AZD-1134 are presumably due to blockade of inhibitory presynaptic 5-HT1B autoreceptors. AZD-1134 administered alone produced antidepressant-like effects in animals.

AZD-1134 reached preclinical research prior to the discontinuation of its development. It was under development by AstraZeneca. Another selective serotonin 5-HT1B receptor antagonist, AZD-3783, was also subsequently developed and studied by AstraZeneca. However, this drug was later found to produce unexpected neurotoxicity.

References

  1. ^ "AZD 1134". AdisInsight. 31 March 2004. Retrieved 11 December 2024.
  2. ^ Hudzik, T.; Smolka, J.; Litwin, L.; Porrey, T.; Pierson, E. (2003). "P.1.016 In vivo pharmacology of AZD1134, a novel 5-HT1B antagonist". European Neuropsychopharmacology. 13: S181–S182. doi:10.1016/S0924-977X(03)91727-5.
  3. ^ Smagin, G.N.; Song, D.; Cross, A.J.; Mrzljak, L. (2003). "P.1.094 AZD1134, a high affinity 5-HT1B receptor antagonist activates serotonin turnover and release in guinea pig brain". European Neuropsychopharmacology. 13: S214. doi:10.1016/S0924-977X(03)91804-9.
  4. Maier DL, Sobotka-Briner C, Ding M, Powell ME, Jiang Q, Hill G, Heys JR, Elmore CS, Pierson ME, Mrzljak L (July 2009). "AZ10419369 binding to the 5-HT1B receptor: in vitro characterization and in vivo receptor occupancy". J Pharmacol Exp Ther. 330 (1): 342–351. doi:10.1124/jpet.109.150722. PMID 19401496.
  5. Zhang M, Zhou D, Wang Y, Maier DL, Widzowski DV, Sobotka-Briner CD, Brockel BJ, Potts WM, Shenvi AB, Bernstein PR, Pierson ME (November 2011). "Preclinical pharmacology and pharmacokinetics of AZD3783, a selective 5-hydroxytryptamine 1B receptor antagonist". J Pharmacol Exp Ther. 339 (2): 567–578. doi:10.1124/jpet.110.174433. PMID 21825000.
  6. Varnäs K, Nyberg S, Karlsson P, Pierson ME, Kågedal M, Cselényi Z, McCarthy D, Xiao A, Zhang M, Halldin C, Farde L (February 2011). "Dose-dependent binding of AZD3783 to brain 5-HT1B receptors in non-human primates and human subjects: a positron emission tomography study with AZ10419369". Psychopharmacology (Berl). 213 (2–3): 533–545. doi:10.1007/s00213-011-2165-z. PMID 21234549.
  7. Chang JC, Ciaccio P, Schroeder P, Wright L, Westwood R, Berg AL (April 2014). "Pathology and Neurotoxicity in Dogs after Repeat Dose Exposure to a Serotonin 5-HT1B Inhibitor". J Toxicol Pathol. 27 (1): 31–42. doi:10.1293/tox.2013-0033. PMC 4000071. PMID 24791065.


Serotonin receptor modulators
5-HT1
5-HT1A
5-HT1B
5-HT1D
5-HT1E
5-HT1F
5-HT2
5-HT2A
5-HT2B
5-HT2C
5-HT3–7
5-HT3
5-HT4
5-HT5A
5-HT6
5-HT7


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