α(1)-Adrenergic Receptors: Insights into Potential Therapeutic Opportunities for COVID-19, Heart Failure, and Alzheimer’s Disease

α(1)-Adrenergic receptors (ARs) are members of the G-Protein Coupled Receptor superfamily and with other related receptors (β and α(2)), they are involved in regulating the sympathetic nervous system through binding and activation by norepinephrine and epinephrine. Traditionally, α(1)-AR antagonists were first used as anti-hypertensives, as α(1)-AR activation increases vasoconstriction, but they are not a first-line use at present. The current usage of α(1)-AR antagonists increases urinary flow in benign prostatic hyperplasia. α(1)-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 α(1)-AR. In this review, we highlight newer treatment potential for α(1A)-AR agonists (heart failure, ischemia, and Alzheimer’s disease) and non-selective α(1)-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.