AZD-1134


AZD-1134 is an investigational new drug that was being evaluated for the treatment of major depressive disorder and anxiety disorders but was never marketed.

Pharmacology

AZD-1134 is a selective serotonin 5-HT1B receptor antagonist. It has been found to increase serotonin levels in the dorsal hippocampus in animals and to increase serotonin turnover 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 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.