AZD-1134 is an investigational new drug that was being evaluated for the treatment of major depressive disorder and anxiety disorder but was never marketed. It is a selective serotonin 5-HT1B receptor antagonist.
Pharmacology.
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.
History.
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.