I and my team of collaborators investigate the CNS noradrenergic system and the alpha-1 adrenoreceptor (AR) specifically as potential therapeutic targets for treatment of behavioral disorders with hyperarousal as a major component of their clinical presentations. These disorders include PTSD, alcohol use disorder, agitation/aggression in dementia and (unexpectedly) post-mild traumatic brain injury migraine-like headaches.
1. PTSD: Based on our clinical observation and data from other laboratories suggesting increased CNS noradrenergic activity in PTSD, we (Drs. Peskind, Petrie, McFall and Army colleagues) demonstrated in three RCTs in combat veterans and active duty soldiers that the CNS active alpha-1 AR antagonist prazosin is effective for PTSD sleep disruption, trauma nightmares, daytime hyperarousal symptoms and global clinical status. Based on these studies, approximately 100,000 military veterans across the US were prescribed prazosin for PTSD in 2013.
2. Alcohol Use Disorder: Based (again) on clinical observation of alcoholic combat veterans achieving long-term abstinence with prazosin treatment, we have demonstrated (with Dr. Rasmussen) in rodent studies that prazosin reduces alcohol consumption in genetically “alcoholic” P rats, and this effect is greater when prazosin is combined with propranolol or naltrexone; and in two RCTs (Simpson, Saxon) that prazosin effectively reduces alcohol consumption in persons with alcohol dependence with or without comorbid PTSD.
3. Dementia Agitation/Aggression: Although locus ceruleus (LC) neurons are lost in Alzheimer’s disease (AD), we demonstrated normal or increased norepinephrine in CSF in AD (Peskind) and increased tyrosine hydroxylase mRNA/LC neuron in AD postmortem tissue and increased alpha-1 AR density in LC projection areas (Szot) in AD. In a pilot RCT (Peskind, Wang) prazosin was effective for agitation/aggression in AD outpatients and nursing home residents.
(2021 Jan 14)
Int J Environ Res Public Health 18(2):
Daniels RD, Clouston SAP, Hall CB, Anderson KR, Bennett DA, Bromet EJ, Calvert GM, Carreón T, DeKosky ST, Diminich ED, Finch CE, Gandy S, Kreisl WC, Kritikos M, Kubale TL, Mielke MM, Peskind ER, Raskind MA, Richards M, Sano M, Santiago-Colón A, Sloan RP, Spiro A 3rd, Vasdev N, Luft BJ, Reissman DB
(2020 Dec 16)
Schindler AG, Terry GE, Wolden-Hanson T, Cline M, Park M, Lee J, Yagi M, Meabon JS, Peskind ER, Raskind MM, Phillips PEM, Cook DG
(2020 Oct 15)
J Neurol Sci 417(): 117049
Meabon JS, Cook DG, Yagi M, Terry GE, Cross DJ, Muzi M, Pagulayan KF, Logsdon AF, Schindler AG, Ghai V, Wang K, Fallen S, Zhou Y, Kim TK, Lee I, Banks WA, Carlson ES, Mayer C, Hendrickson RC, Raskind MA, Marshall DA, Perl DP, Keene CD, Peskind ER
(2020 Jun 10)
Sci Rep 10(1): 9420
Logsdon AF, Schindler AG, Meabon JS, Yagi M, Herbert MJ, Banks WA, Raskind MA, Marshall DA, Keene CD, Perl DP, Peskind ER, Cook DG
Sleep Med Rev 50(): 101272
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