AZD-3783 is a serotonin 5-HT1B receptor antagonist which was under development for the treatment of major depressive disorder and anxiety disorders.[1][2][3][4][5] It was being developed by AstraZeneca.[1][2] The drug reached phase 1 clinical trials prior to the discontinuation of its development.[1][2] It was discontinued following unexpected neurotoxicity findings in animals.[6]

See also

References

  1. ^ a b c d "AZD 3783". AdisInsight. 18 December 2007. Retrieved 28 February 2025.
  2. ^ a b c "Delving into the Latest Updates on AZD-3783 with Synapse". Synapse. 23 January 2025. Retrieved 28 February 2025.
  3. ^ Tiger M, Varnäs K, Okubo Y, Lundberg J (May 2018). "The 5-HT1B receptor - a potential target for antidepressant treatment". Psychopharmacology. 235 (5): 1317–1334. doi:10.1007/s00213-018-4872-1. PMC 5919989. PMID 29546551. 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.
  4. ^ 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". The Journal of Pharmacology and Experimental Therapeutics. 339 (2): 567–578. doi:10.1124/jpet.110.174433. PMID 21825000.{{cite journal}}: CS1 maint: overridden setting (link)
  5. ^ 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. 213 (2–3): 533–545. doi:10.1007/s00213-011-2165-z. PMID 21234549.{{cite journal}}: CS1 maint: overridden setting (link)
  6. ^ 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". Journal of Toxicologic Pathology. 27 (1): 31–42. doi:10.1293/tox.2013-0033. PMC 4000071. PMID 24791065.
Allikas: https://en.wikipedia.org/wiki/AZD-3783
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