ArticlePLoS neglected tropical diseases2017
Cyclobenzaprine Raises ROS Levels in Leishmania infantum and Reduces Parasite Burden in Infected Mice.
Article in PLoS neglected tropical diseases, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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.
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.
Who cites it
14 citing papers in PubMed, 23 citations in OpenAlex.
- Oxidative Stress and Survival ofExpert reviews in molecular medicine · 2025Review
- The impact of tizanidine, thiocolchicoside, and cyclobenzaprine on vascular function in ovariectomized rats.Turkish journal of medical sciences · 2025Article
- Anti-Antimicrobial agents and chemotherapy · 2024Article
- Article
- Article
- Genetic haplotypes associated with immune response to Leishmania infantum infection in dogs.Veterinary research communications · 2023Article
- Effect of Itraconazole-Ezetimibe-Miltefosine Ternary Therapy in Murine Visceral Leishmaniasis.Antimicrobial agents and chemotherapy · 2023Article
- Chalcones identify cTXNPx as a potential antileishmanial drug target.PLoS neglected tropical diseases · 2021Article
- Quinolizidine-Derived Lucanthone and Amitriptyline Analogues Endowed with Potent Antileishmanial Activity.Pharmaceuticals (Basel, Switzerland) · 2020Article
- Prolyl Oligopeptidase FromFrontiers in microbiology · 2020Article
- Exploiting knowledge on pharmacodynamics-pharmacokinetics for accelerated anti-leishmanial drug discovery/development.Expert opinion on drug metabolism & toxicology · 2019Review
- Synthesis and Leishmanicidal Activity of Novel Urea, Thiourea, and Selenourea Derivatives of Diselenides.Antimicrobial agents and chemotherapy · 2019Article
- Miltefosine-Lopinavir Combination Therapy AgainstFrontiers in cellular and infection microbiology · 2019Article
- Molecular Basis of the Leishmanicidal Activity of the Antidepressant Sertraline as a Drug Repurposing Candidate.Antimicrobial agents and chemotherapy · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe leishmanicidal action of tricyclic antidepressants has been studied and evidences have pointed that their action is linked to inhibition of trypanothione reductase, a key enzyme in the redox metabolism of pathogenic trypanosomes. Cyclobenzaprine (CBP) is a tricyclic structurally related to the antidepressant amitriptyline, differing only by the presence of a double bond in the central ring. This paper describes the effect of CBP in experimental visceral leishmaniasis, its inhibitory effect in trypanothione reductase and the potential immunomodulatory activity. METHODOLOGY/PRINCIPAL
findingsIn vitro antileishmanial activity was determined in promastigotes and in L. infantum-infected macrophages. For in vivo studies, L. infantum-infected BALB/c mice were treated with CBP by oral gavage for five days and the parasite load was estimated. Trypanothione reductase activity was assessed in the soluble fraction of promastigotes of L. infantum. For evaluation of cytokines, L. infantum-infected macrophages were co-cultured with BALB/c splenocytes and treated with CBP for 48 h. The supernatant was analyzed for IL-6, IL-10, MCP-1, IFN-γ and TNF-α. CBP demonstrated an IC50 of 14.5±1.1μM and an IC90 of 74.5±1.2 μM in promastigotes and an IC50 of 12.6±1.05 μM and an IC90 of 28.7±1.3 μM in intracellular amastigotes. CBP also reduced the parasite load in L. infantum-infected mice by 40.4±10.3% and 66.7±10.5% in spleen at 24.64 and 49.28 mg/kg, respectively and by 85.6±5.0 and 89.3±4.8% in liver at 24.64 and 49.28mg/kg, after a short-term treatment. CBP inhibited the trypanothione reductase activity with a Ki of 86 ± 7.7 μM and increased the ROS production in promastigotes. CBP inhibited in 53% the production of IL-6 in infected macrophages co-culture. CONCLUSION/SIGNIFICANCE: To the best of our knowledge, this study is the first report of the in vivo antileishmanial activity of the FDA-approved drug CBP. Modulation of immune response and induction of oxidative stress in parasite seem to contribute to this efficacy.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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 OpenQuestion graph.