Prazosin, a drug that prevents the neurotransmitter norepinephrine from binding to its alpha1 receptor (alpha1-AR) subtype has shown efficacy in reducing PTSD symptoms in most, but not all, studies of trauma-exposed Service Members, Veterans, and civilians. However, it is not effective in all patients and its use is complicated by variability in effective doses, a short duration of action, and frequent orthostatic hypotension at dose initiation.
We propose to develop a fluorine-18-labeled radiotracer for PET imaging of brain alpha1A-ARs (implicated in the pathophysiology of PTSD) in human subjects so as to create a PET-based method to identify alpha1A-AR blocking drugs that are more broadly effective and lack the shortcomings of prazosin. Displacement of radiotracer binding by drug candidates will allow assessment of their actions at brain alpha1A-ARs and facilitate the development of novel PTSD therapeutics.
June 1, 2020 — May 31, 2023