{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T06:46:37Z","timestamp":1787035597948,"version":"build-2736575974"},"reference-count":99,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T00:00:00Z","timestamp":1758585600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the National Institute of Aging","award":["RO1AG066627"],"award-info":[{"award-number":["RO1AG066627"]}]},{"name":"the Alzheimer\u2019s Drug Discovery Foundation (ADDF)-Program to Accelerate Clinical Trials (PACT)","award":["RO1AG066627"],"award-info":[{"award-number":["RO1AG066627"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Decades ago, previous studies that used non-selective ergot derivatives suggested that blockage of the \u03b11A-adrenergic receptor mildly increased cognition through increased blood flow to the brain due to vasodilation and, thus, could be used as a treatment for dementia. However, further studies indicated that nicergoline was non-specific and hit many different targets. Today, a similar scenario is developing with the use of non-selective \u03b11-AR antagonists of the quinazoline class, referred to as \u201cosins\u201d, as potential treatments for COVID-19\/SARS, post-traumatic stress disorder, cancer, and neurodegenerative disorders, such as Parkinson\u2019s, Alzheimer\u2019s, and amyotrophic lateral sclerosis. While there is extensive evidence of neuroprotection from many clinical trials, the mechanism of action of quinazolines is often not \u03b11-AR-mediated but keyed to its glycolysis-enhancing effects through activation of the enzyme phosphoglycerate kinase 1 (PGK1). These studies have incorrectly labeled the \u03b11A-adrenergic receptor as an \u201cold target\u201d to treat Alzheimer\u2019s and other neurocognitive diseases, hampering drug development. This review will summarize these and other studies to indicate that activation, not blockage, of norepinephrine\u2019s actions, through \u03b11A-AR, mediates cognitive, memory, and neuroprotective functions that may reverse the progression of neurocognitive diseases.<\/jats:p>","DOI":"10.3390\/ph18101425","type":"journal-article","created":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T08:09:42Z","timestamp":1758614982000},"page":"1425","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["\u03b11A-Adrenergic Receptor as a Target for Neurocognition: Cautionary Tale from Nicergoline and Quinazoline Non-Selective Blockers"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1790-5776","authenticated-orcid":false,"given":"Dianne M.","family":"Perez","sequence":"first","affiliation":[{"name":"Department of Cardiovascular & Metabolic Sciences, Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Ave, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2005589","DOI":"10.1155\/2024\/2005589","article-title":"The \u03b23-Adrenergic Receptor: Structure, Physiopathology of Disease, and Emerging Therapeutic Potential","volume":"2024","author":"Dongdem","year":"2024","journal-title":"Adv. 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