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AZD-1134

From Wikipedia, the free encyclopedia

Pharmaceutical compound
AZD-1134
Clinical data
Routes of
administration		Unspecified[1]
Drug classSerotonin5-HT1B receptorantagonist
Identifiers
  • 6-fluoro-8-(4-methylpiperazin-1-yl)-4-oxo-N-[4-(4-propanoylpiperazin-1-yl)phenyl]chromene-2-carboxamide
CAS Number
PubChemCID
ChemSpider
UNII
ChEMBL
Chemical and physical data
FormulaC28H32FN5O4
Molar mass521.593 g·mol−1
3D model (JSmol)
  • 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=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 aninvestigational new drug that was being evaluated for the treatment ofmajor depressive disorder andanxiety disorder but was never marketed.[1][2][3][4] It is aselectiveserotonin5-HT1B receptorantagonist.

Pharmacology

[edit]

The drug has been found to increaseserotonin levels in thedorsal hippocampus in animals and to increase serotoninturnover (as measured by5-HIAA/serotonin ratio) in thecerebral cortex,hypothalamus,hippocampus, andstriatum.[3] Alone, AZD-1134 increased hippocampal serotonin levels to 179% of baseline, and in combination with theselective serotonin reuptake inhibitor (SSRI)citalopram, it increased levels to 950% of baseline.[3] The increases in serotonin levels and turnover with AZD-1134 are presumably due to blockade ofinhibitorypresynaptic 5-HT1Bautoreceptors.[3] AZD-1134 administered alone producedantidepressant-like effects in animals.[2]

History

[edit]

AZD-1134 reachedpreclinical research prior to the discontinuation of its development.[1] It was under development byAstraZeneca.[1] Another selective serotonin 5-HT1B receptor antagonist,AZD-3783, was also subsequently developed and studied by AstraZeneca.[5][6] However, this drug was later found to produce unexpectedneurotoxicity.[7]

References

[edit]
  1. ^abcd"AZD 1134".AdisInsight. 31 March 2004. Retrieved11 December 2024.
  2. ^abHudzik 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. ^abcdSmagin GN, Song D, Cross AJ, Mrzljak (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, et al. (July 2009). "[N-methyl-3H3]AZ10419369 binding to the 5-HT1B receptor: in vitro characterization and in vivo receptor occupancy".The Journal of Pharmacology and Experimental Therapeutics.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, et al. (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, et al. (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 [11C]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.


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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