Evidence map›Paper›PMID 41589494›Full record

ArticleCNS & neurological disorders drug targets2026

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

Alberto Souza Sa Filho, Rafael Fernandes Costa, Emanuelly Karla Araujo Padilha, Edeildo Ferreira da Silva-Junior, Gustavo Pedrino Rodrigues, Denise da Silva Pinheiro, Hamilton Barbosa Napolitano, Sergio Machado, Vicente Aprigliano, Jose Luis Rodrigues Martins and 2 more

Abstract read
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Article in CNS & neurological disorders drug targets, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Alberto Souza Sa FilhoGraduate Program in Pharmaceutical Sciences, Campus Arthur Wesley Archibald, Evangelical University of Goiás, Anápolis, 75083-515, Brazil.
Rafael Fernandes CostaGraduate Program in Pharmaceutical Sciences, Campus Arthur Wesley Archibald, Evangelical University of Goiás, Anápolis, 75083-515, Brazil.ORCID 0000-0002-2431-6371
Emanuelly Karla Araujo PadilhaResearch Group in Biological and Molecular Chemistry, Institute of Chemistry and Biotechnology, Federal University of Alagoas, Lourival Melo Mota Avenue, AC, Simões Campus, 57072-900, Maceió, Brazil.ORCID 0009-0002-3932-9068
Edeildo Ferreira da Silva-JuniorResearch Group in Biological and Molecular Chemistry, Institute of Chemistry and Biotechnology, Federal University of Alagoas, Lourival Melo Mota Avenue, AC, Simões Campus, 57072-900, Maceió, Brazil.ORCID 0000-0002-1527-4501
Gustavo Pedrino RodriguesInstitute of Biological Sciences, Federal University of Goiás, Campus Samambaia, Goiânia, GO, Brazil.ORCID 0000-0003-0488-5400
Denise da Silva PinheiroInstitute of Biological Sciences, Federal University of Goiás, Campus Samambaia, Goiânia, GO, Brazil.ORCID 0000-0001-7405-6822
Hamilton Barbosa NapolitanoGraduate Program in Pharmaceutical Sciences, Campus Arthur Wesley Archibald, Evangelical University of Goiás, Anápolis, 75083-515, Brazil.ORCID 0000-0002-6047-9995
Sergio MachadoLaboratory of Panic and Respiration, Institute of Psychiatry (IPUB), Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil.ORCID 0000-0001-8946-8467
Vicente ApriglianoEscuela de Ingeniería de Construcción y Transporte, Pontificia Universidad Católica de Valparaíso, Avda Brasil 2147, Valparaíso, Postal Code: 2362804, Chile.ORCID 0000-0002-7285-2742
Jose Luis Rodrigues MartinsGraduate Program in Pharmaceutical Sciences, Campus Arthur Wesley Archibald, Evangelical University of Goiás, Anápolis, 75083-515, Brazil.ORCID 0000-0003-3516-5350
Antonio Sergio Nakao de AguiarGraduate Program in Pharmaceutical Sciences, Campus Arthur Wesley Archibald, Evangelical University of Goiás, Anápolis, 75083-515, Brazil.ORCID 0000-0001-9410-9194
James Oluwagbamigbe FajemiroyeGraduate Program in Pharmaceutical Sciences, Campus Arthur Wesley Archibald, Evangelical University of Goiás, Anápolis, 75083-515, Brazil.ORCID 0000-0001-7440-7581

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionAnxiety 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.

methods60 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.

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

conclusionEnalapril demonstrates anxiolytic-like properties, further insights into the GABAergicrenin- angiotensin-aldosterone mechanistic hypothesis.

Indexed as

Anti-Anxiety AgentsAnxietyEnalaprilAdministration, OralAnimalsDiazepamExploratory BehaviorLosartanMaleMiceMolecular Docking SimulationPropranololAnti-Anxiety AgentsDiazepamEnalaprilLosartanPropranololanxietybinding sitebiological stressdrug evaluationHypertensionpharmacology

Identifiers

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.