Objectives: Anxiety and adjustment disorders are among the most prevalent mental health conditions. This review focuses on γ-aminobutyric acid receptor type A (GABAAR)-mediated anxiolysis, describing the action of both endogenous and exogenous modulators of GABAAR. Future directions and innovative strategies to alleviate anxiety symptoms are discussed, with a particular emphasis on etifoxine.
Methods: We used available data from the recent literature to update the mode of action of anxiolytics. We focussed our search on anxiolytics acting at GABAARs, as well as on the pharmacological properties of formerly and currently prescribed anxiolytics.
Results: Considering the adverse effects of current treatments aimed at increasing inhibitory controls, optimisation of existing pharmacotherapies is of crucial importance. Among the alternative compounds targeting the GABAergic system, translocator protein (TSPO) ligands, such as etifoxine (EFX), which promote endogenous neurosteroidogenesis, are emerging as promising candidates for anxiety relief. In several papers comparing the efficacy of benzodiazepines and EFX, EFX showed interesting properties with limited side effects. Indeed, neurosteroids are potent GABAAR modulators with highly underrated anxiolytic properties.
Conclusions: Novel therapeutic strategies have been emerging following the recognition of neurosteroids as potent anxiolytics. Featured at the top of the list for well-tolerated anxiety relief, TSPO ligands such as etifoxine appear promising.
Keywords: Anxiety; barbiturates; benzodiazepines; inhibition; neurosteroids.