α1-Adrenergic Receptors: Insights into Potential Therapeutic Opportunities for COVID-19, Heart Failure, and Alzheimer’s Disease

• Published in: International journal of molecular sciences Vol. 24; no. 4; p. 4188
• Main Author: Perez, Dianne M.
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 20.02.2023; MDPI
• Subjects: Adrenergic receptors; Agonists; alpha adrenergic; Alzheimer's disease; Alzheimer’s; Animal models; Antagonists; Bias; Blood pressure; Cell lines; Clinical trials; Cloning; Cognition & reasoning; Congestive heart failure; COVID-19; Drug development; Epinephrine; G protein-coupled receptors; Glucose; GPCR; Heart attacks; Heart failure; Hyperplasia; Ischemia; Kinases; Ligands; Memory; Metabolism; Norepinephrine; Parkinson's disease; Physiology; Post traumatic stress disorder; Proteins; Receptors (physiology); Review; Septic shock; Signal transduction; Smooth muscle; Sympathetic nervous system; therapeutics; Transgenic animals; Vasoconstriction
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24044188

α1-Adrenergic receptors (ARs) are members of the G-Protein Coupled Receptor superfamily and with other related receptors (β and α2), they are involved in regulating the sympathetic nervous system through binding and activation by norepinephrine and epinephrine. Traditionally, α1-AR antagonists were first used as anti-hypertensives, as α1-AR activation increases vasoconstriction, but they are not a first-line use at present. The current usage of α1-AR antagonists increases urinary flow in benign prostatic hyperplasia. α1-AR agonists are used in septic shock, but the increased blood pressure response limits use for other conditions. However, with the advent of genetic-based animal models of the subtypes, drug design of highly selective ligands, scientists have discovered potentially newer uses for both agonists and antagonists of the α1-AR. In this review, we highlight newer treatment potential for α1A-AR agonists (heart failure, ischemia, and Alzheimer’s disease) and non-selective α1-AR antagonists (COVID-19/SARS, Parkinson’s disease, and posttraumatic stress disorder). While the studies reviewed here are still preclinical in cell lines and rodent disease models or have undergone initial clinical trials, potential therapeutics discussed here should not be used for non-approved conditions.