Synonyms: Prazosin hydrochloride, Minipress, Hypovase, Vasoflex
Therapy Type: Small Molecule (timeline)
Target Type: Other Neurotransmitters (timeline)
Condition(s): Alzheimer's Disease
U.S. FDA Status: Alzheimer's Disease (Phase 4)
Approved for: Hypertension
Prazosin is an α-blocker, that is, an antagonist selective for α-1
(e.g., Haase et al., 2013).
In an initial study conducted through the University of Washington in Seattle, 22 people with AD and aggressive agitation were randomized to take up to 6 mg/day of prazosin or placebo a day for eight weeks and evaluated on overall global impression of change and the neuropsychiatric inventory (NPI). Prazosin outperformed placebo in this pilot study (Wang et al., 2009).
In 2010, a second NIH-funded study at the University of Washington started to recruit 120 patients with AD and disruptive agitation to compare a 12-week course of 8 mg/day of prazosin to placebo followed by 12 weeks of prazosin offered open-label. In 2013, the NIH announced that it would fund a multicenter North American study of prazosin through the Alzheimer's Disease Cooperative Study’s national consortium of academic medical centers (ADCS) (Jan 2013 news story).
Research Models Citations
- Wang LY, Shofer JB, Rohde K, Hart KL, Hoff DJ, McFall YH, Raskind MA, Peskind ER. Prazosin for the treatment of behavioral symptoms in patients with Alzheimer disease with agitation and aggression. Am J Geriatr Psychiatry. 2009 Sep;17(9):744-51. PubMed.
- Shimohama S, Taniguchi T, Fujiwara M, Kameyama M. Biochemical characterization of alpha-adrenergic receptors in human brain and changes in Alzheimer-type dementia. J Neurochem. 1986 Oct;47(4):1295-301. PubMed.
- Szot P, White SS, Greenup JL, Leverenz JB, Peskind ER, Raskind MA. Compensatory changes in the noradrenergic nervous system in the locus ceruleus and hippocampus of postmortem subjects with Alzheimer's disease and dementia with Lewy bodies. J Neurosci. 2006 Jan 11;26(2):467-78. PubMed.
- Katsouri L, Vizcaychipi MP, McArthur S, Harrison I, Suárez-Calvet M, Lleo A, Lloyd DG, Ma D, Sastre M. Prazosin, an α(1)-adrenoceptor antagonist, prevents memory deterioration in the APP23 transgenic mouse model of Alzheimer's disease. Neurobiol Aging. 2013 Apr;34(4):1105-15. Epub 2012 Oct 11 PubMed.
- Haase N, Herse F, Spallek B, Haase H, Morano I, Qadri F, Szijártó IA, Rohm I, Yilmaz A, Warrington JP, Ryan MJ, Gollasch M, Müller DN, Dechend R, Wallukat G. Amyloid-β peptides activate α1-adrenergic cardiovascular receptors. Hypertension. 2013 Nov;62(5):966-72. Epub 2013 Sep 3 PubMed.
- Ballard C, Corbett A. Agitation and aggression in people with Alzheimer's disease. Curr Opin Psychiatry. 2013 May;26(3):252-9. PubMed.
- Sharp SI, Ballard CG, Chen CP, Francis PT. Aggressive behavior and neuroleptic medication are associated with increased number of alpha1-adrenoceptors in patients with Alzheimer disease. Am J Geriatr Psychiatry. 2007 May;15(5):435-7. PubMed.
- Kalaria RN. Characterization of [125I]HEAT binding to alpha 1-receptors in human brain: assessment in aging and Alzheimer's disease. Brain Res. 1989 Nov 6;501(2):287-94. PubMed.
- O'Neill C, Fowler CJ, Winblad B. Alpha 1-adrenergic receptor binding sites in post-mortal human cerebral microvessel preparations: preservation in multi-infarct dementia and dementia of Alzheimer type. J Neural Transm Park Dis Dement Sect. 1989;1(4):303-10. PubMed.