ANXIOLYTICS: Origins, drug discovery, and mechanisms.

Autor: Witkin JM; Laboratory of Antiepileptic Drug Discovery, Ascension St. Vincent Hospital, Indianapolis, IN, USA. Electronic address: witkinconsult@gmail.com., Barrett JE; Center for Substance Abuse Research, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA. Electronic address: jebarrett@temple.edu.
Jazyk: angličtina
Zdroj: Pharmacology, biochemistry, and behavior [Pharmacol Biochem Behav] 2024 Dec; Vol. 245, pp. 173858. Date of Electronic Publication: 2024 Aug 22.
DOI: 10.1016/j.pbb.2024.173858
Abstrakt: Anxiety is a part of the human condition and has been managed by psychoactive substances for centuries. The current medical need and societal demand for anxiolytic medicines has not abated. The present overview provides a brief historical introduction to the discovery of modern age anxiolytics that include the benzodiazepines together with a discussion of the continuing medical need for new antianxiety medications. The paper also discusses the use and impact of behavioral pharmacology in the preclinical development of anxiolytics. The review then highlights the diversity of mechanisms for creating a new generation of anxiolytics through mechanisms beyond the potentiation of GABA A receptors and the blockade of monoamine uptake. A discussion then follows on the behavioral specificity of action of anxiolytics that includes the concept of creating an anxioselective drug, one that targets anxiety without producing untoward effects that include sedation and dependence. The use of anxiolytics in the treatment of other conditions such as substance use disorder is also briefly reviewed. Finally, a brief summary of the current status of anxiolytic drug development is provided. The review concludes with the idea that despite a host of anxiolytic drugs, the lack of efficacy in some patients and the side-effects and safety issues associated with some of these medications demands alternative medicines. Current preclinical and clinical research is ongoing with the goal of identifying such compounds.
Competing Interests: Declaration of competing interest The authors have no conflicts of interest.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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