spec sheet8 rows
AZD-3783 is an investigational, selective serotonin 5-HT1B receptor antagonist that AstraZeneca developed as a potential treatment for major depressive and anxiety disorders.
- Confirmed target engagement of brain 5-HT1B receptors by PET imaging in humans
- Pharmacokinetics translated predictably from animals to a human single-dose study
- Caused serious neurotoxicity in dogs during repeat-dose animal testing
Overview
A serotonin drug that engaged its target well in human PET scans, but repeat-dose animal testing turned up nerve damage serious enough to end the program.
Mechanism
AZD-3783 selectively blocks the 5-HT1B receptor, a presynaptic autoreceptor whose blockade is intended to raise brain serotonin availability. PET imaging with the radiotracer [11C]AZ10419369 confirmed dose-dependent occupancy of brain 5-HT1B receptors in both non-human primates and human subjects, and its pharmacokinetics translated well from animal models to a single 20 mg oral dose in healthy volunteers.
receptor fingerprint
5-HT1B receptorAntagonist
Safetyrisks and cautions, not medical advice
Development was discontinued after repeat-dose toxicology in dogs found significant neurotoxicity. A one-month study produced neuronal vacuolation, liver enzyme elevation with hepatocellular damage, and gallbladder changes at high doses, while a three-month study caused degenerative changes in the retina, brain, spinal ganglia, and peripheral nerves severe enough to require euthanizing one animal, ending the program after only Phase I testing in humans.
Subjective profileweighing the evidence above
A cautionary tale rather than a candidate. It proved it engaged its target in human brains, then three months of repeat dosing in dogs produced degeneration in retina, brain and peripheral nerves severe enough to end the program. The target may still be worth chasing; this molecule is not.
Resources
This entry is here for reference.
Research
- 2011first citedPreclinical pharmacology and pharmacokinetics of AZD3783, a selective 5-hydroxytryptamine 1B re…
- 2014most recentPathology and Neurotoxicity in Dogs after Repeat Dose Exposure to a Serotonin 5-HT1B Inhibitor
- 1.Preclinical pharmacology and pharmacokinetics of AZD3783, a selective 5-hydroxytryptamine 1B receptor antagonist
- 2.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
- 3.Pathology and Neurotoxicity in Dogs after Repeat Dose Exposure to a Serotonin 5-HT1B Inhibitor
3 listed here; entry last updated July 2026
Reviews
My notesprivate to this device
FAQ
What is AZD-3783 used for?
It was researched as a potential treatment for major depressive disorder and anxiety disorders.
How does AZD-3783 work?
It blocks the 5-HT1B serotonin autoreceptor, which is meant to raise brain serotonin levels; note it is a 5-HT1B antagonist, not a 5-HT1A antagonist as it is sometimes mislabeled.
Is AZD-3783 well-researched?
It has solid preclinical and PET imaging data confirming it hits its target, but repeat-dose animal toxicology found serious nerve damage, which ended development after Phase I.
Adverse effects
- Caused serious neurotoxicity in dogs during repeat-dose animal testing
Notes and cautions
- Development was stopped after Phase I because of this safety signal