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image of Putative Antianxiety Property of Oral Enalapril Formulation in Mice: a Preclinical and in silico Study

Abstract

Introduction

Anxiety disorders, characterized by overwhelming fear, affect more than 30% of the global population. Recent evidence indicates that antihypertensive medications could offer symptomatic relief for anxiety, supporting their potential for repurposing. The objective is to investigate the anxiolytic-like effects of an enalapril formulation.

Methods

60 Swiss mice (30 ± 5 g, aged 6-8 weeks) were randomly assigned to groups and received oral treatments with either vehicle (10 mL/kg), diazepam (DZP, 5 mg/kg), reference enalapril (ENAR), enalapril formulation (ENAF), losartan (LOS), or propranolol (PRO), each at a dose of 10 mg/kg. After 60 minutes, the animals were exposed to 5 minutes of exploratory activity in the open field, elevated plus maze (EPM), light-dark box (LDB), and a minute of rotarod.

Results

One-way ANOVA demonstrated differences for the total crossing (0.0001), freezing time (0.0001), number of rearing (0.002), time spent (0.002), and crossing at the center (0.0001) of the open field. Unlike in the rotarod (>0.05), the ENAR, ENAF, LOS, and PRO elicit increases (0.05) in the total number of arm entries and time spent on the open arms of EPM while increasing the number of transitions (0.05) and time spent in the light area of the LDB (0.001). screening suggests stability of interaction with several amino acid residues overlapping with the flumazenil binding site, with the binding energy (Δ = −22.59kcal/mol towards the benzodiazepine binding site (flumazenil Δ = −43.92kcal/mol).

Discussion

The repositioning of drugs available to the population is an interesting approach toward the discovery of alternative or add-on treatments for anxiety. Ongoing resort to repurposing, reusing, reprofiling, and rediscovery of “old” drugs for a new indication seems to be an interesting way out of failures, the expensive and slow pace of new drug discovery.

Conclusion

Enalapril demonstrates anxiolytic-like properties, further insights into the GABAergic-renin-angiotensin-aldosterone mechanistic hypothesis.

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2026-01-23
2026-01-29

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Putative Antianxiety Property of Oral Enalapril Formulation in Mice: a Preclinical and in silico Study
Bentham Science Publishers ; https://doi.org/10.2174/0118715273375375251114045754
/content/journals/cnsnddt/10.2174/0118715273375375251114045754
/content/journals/cnsnddt/10.2174/0118715273375375251114045754
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  • Article Type:     Research Article
Keywords: binding site ; Hypertension ; biological stress ; drug evaluation ; anxiety ; pharmacology

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