Journal: Frontiers in Pharmacology

Article Title: Repurposing memantine as an oral therapy for visceral leishmaniasis: identification of direct leishmanicidal activity and immune system modulation in preclinical studies

doi: 10.3389/fphar.2026.1761504

Figure Lengend Snippet: Cytotoxic effect of memantine on murine peritoneal macrophages. Murine peritoneal macrophages were plated and incubated with increasing concentrations of memantine (ranging from 3.9 μM to 8 mM) for 72 h in the absence of infection. Cell viability was assessed using resazurin. The values are presented as the means ± standard errors of three independent experiments (n = 3) performed in triplicate. * indicates a significant difference compared with the control (p ≤ 0.05); ** indicates a significant difference compared with the control (p ≤ 0.01); *** indicates a significant difference compared with the control (p ≤ 0.001); **** indicates a significant difference compared with the control (p ≤ 0.0001).

Article Snippet: Memantine hydrochloride was obtained from Tocris Bioscience (Bristol, UK).

Techniques: Incubation, Infection, Control

Journal: Frontiers in Pharmacology

Article Title: Repurposing memantine as an oral therapy for visceral leishmaniasis: identification of direct leishmanicidal activity and immune system modulation in preclinical studies

doi: 10.3389/fphar.2026.1761504

Figure Lengend Snippet: Effect of memantine on Leishmania infantum- infected macrophages. (A) The infection index was calculated by counting at least 200 macrophages on each duplicated coverslip using light microscopy. All presented values represent the means ± standard errors from three independent experiments (n = 3) performed in duplicate. A significant difference compared with the control is indicated by *p < 0.0001. (B–K) Representative images of murine peritoneal macrophages infected with Leishmania infantum and incubated with memantine. Images were captured at ×200 (left panel) and ×500 (right panel) magnification. Arrows indicate Leishmania infantum -infected macrophages; intracellular amastigotes are indicated by arrowheads. The scale bars correspond to 10 μm. (B,C) Control; (D,E) 4 μM; (F,G) 17 μM; (H,I) 70 μM; (J,K) 280 μM of memantine.

Article Snippet: Memantine hydrochloride was obtained from Tocris Bioscience (Bristol, UK).

Techniques: Infection, Light Microscopy, Control, Incubation

Journal: Frontiers in Pharmacology

Article Title: Repurposing memantine as an oral therapy for visceral leishmaniasis: identification of direct leishmanicidal activity and immune system modulation in preclinical studies

doi: 10.3389/fphar.2026.1761504

Figure Lengend Snippet: Short-term therapeutic effectiveness of memantine in a murine model of visceral leishmaniasis. BALB/c mice were infected with Leishmania infantum promastigotes via intraperitoneal injection. At 7 days post-infection, the mice were treated orally with 1.5, 3 or 6 mg/kg/day of memantine (treated group) or vehicle (control group) or intramuscularly injected with 100 mg/kg/day of meglumine antimoniate (positive control group). After 5 days of treatment (at the end of treatment), the mice were euthanized, and the livers were collected to quantify parasite load via a limiting dilution assay (LDA). A significant difference between control and treated groups is indicated by #p ≤ 0.0001; significant differences between the treated groups are indicated by *p ≤ 0.05 and **p ≤ 0.005. The values are presented as the means ± standard errors of 1 independent experiment with 5 animals per group. Student’s t test with the Mann‒Whitney post hoc test were used for the analysis. Ctrl, control; Sb 5+ , meglumine antimoniate.

Article Snippet: Memantine hydrochloride was obtained from Tocris Bioscience (Bristol, UK).

Techniques: Infection, Injection, Control, Positive Control, Limiting Dilution Assay

Journal: Frontiers in Pharmacology

Article Title: Repurposing memantine as an oral therapy for visceral leishmaniasis: identification of direct leishmanicidal activity and immune system modulation in preclinical studies

doi: 10.3389/fphar.2026.1761504

Figure Lengend Snippet: Long-term therapeutic effectiveness of memantine in a murine model of visceral leishmaniasis. BALB/c mice were infected with Leishmania infantum promastigotes via intraperitoneal injection. At 7 days post-infection, the mice were treated orally with 1.5, 3, or 6 mg/kg/day of memantine (treated group) or vehicle (control group) or intramuscularly injected with 100 mg/kg/day of meglumine antimoniate (positive control group). The mice were euthanized 18 days after the end of treatment, and the livers were collected to quantify parasite load by using a limiting dilution assay (LDA). A significant difference between control and treated groups is indicated by #p ≤ 0.0001; significant differences between the treated groups are indicated by *p ≤ 0.05, **p ≤ 0.005, and ***p ≤ 0.0005. The values are presented as the means ± standard errors of 2 independent experiments with 5 animals per group. Student’s t test with the Mann‒Whitney post hoc test was used for the analysis. Ctrl, control; Sb 5+ , meglumine antimoniate.

Article Snippet: Memantine hydrochloride was obtained from Tocris Bioscience (Bristol, UK).

Techniques: Infection, Injection, Control, Positive Control, Limiting Dilution Assay

Journal: Frontiers in Pharmacology

Article Title: Repurposing memantine as an oral therapy for visceral leishmaniasis: identification of direct leishmanicidal activity and immune system modulation in preclinical studies

doi: 10.3389/fphar.2026.1761504

Figure Lengend Snippet: Modulation of the IFN-γ/IL-10 balance by memantine treatment in Leishmania infantum -infected mice. Splenocytes from infected and uninfected mice were stimulated in vitro with LiAg for 72 h, and cytokine concentrations were measured by using a cytometric bead array (CBA). Data are presented as the IFN-γ/IL-10 ratio, with values above 1 (dotted line) indicating a Th1-skewed profile. The data are presented as means ± standard deviations (SDs) obtained in two independent experiments. *p ≤ 0.05. Ctrl, control; Ctrl ninf, noninfected control; Sb 5+ , meglumine antimoniate.

Article Snippet: Memantine hydrochloride was obtained from Tocris Bioscience (Bristol, UK).

Techniques: Infection, In Vitro, Control

Journal: Frontiers in Pharmacology

Article Title: Repurposing memantine as an oral therapy for visceral leishmaniasis: identification of direct leishmanicidal activity and immune system modulation in preclinical studies

doi: 10.3389/fphar.2026.1761504

Figure Lengend Snippet: Nitrite production by spleen cells stimulated with or without Leishmania antigen (LiAg). Spleen cells were obtained from the supernatant of spleen macerates from mice that were either noninfected or infected with Leishmania infantum and treated with or without memantine or meglumine antimoniate under a long-term treatment regimen. Cells were either unstimulated (BG) or stimulated with soluble Leishmania antigen (LiAg) for 72 h. After the incubation, nitric oxide (NO) production was assessed indirectly by measuring nitrite levels in the culture supernatants using the Griess assay. The data are presented as the means ± standard deviations (SDs) from two independent experiments, each using five animals per group. Ctrl, control; Ctrl ninf, noninfected control; BG, background group (unstimulated); LiAg, Leishmania infantum antigen.

Article Snippet: Memantine hydrochloride was obtained from Tocris Bioscience (Bristol, UK).

Techniques: Infection, Incubation, Griess Assay, Control

Journal: Frontiers in Pharmacology

Article Title: Repurposing memantine as an oral therapy for visceral leishmaniasis: identification of direct leishmanicidal activity and immune system modulation in preclinical studies

doi: 10.3389/fphar.2026.1761504

Figure Lengend Snippet: Heatmap of the Spearman correlation coefficients between the parasite load and the levels of nitric oxide and pro- and anti-inflammatory cytokines. (A) Control; (B) meglumine antimoniate; (C) 1.5 mg/kg/day memantine; (D) 3 mg/kg/day memantine; (E) 6 mg/kg/day memantine. The analysis was performed by determining the correlations between cytokine levels and Leishmania infantum infection (parasite load). Warm colors indicate negative correlations, while cool colors indicate positive correlations. Spearman’s correlation coefficients (p) are represented by the color scale, with statistical significance indicated by asterisks (*p ≤ 0.05 and **p ≤ 0.005). PL, parasite load; NO, nitric oxide.

Article Snippet: Memantine hydrochloride was obtained from Tocris Bioscience (Bristol, UK).

Techniques: Control, Infection

Journal: Frontiers in Pharmacology

Article Title: Repurposing memantine as an oral therapy for visceral leishmaniasis: identification of direct leishmanicidal activity and immune system modulation in preclinical studies

doi: 10.3389/fphar.2026.1761504

Figure Lengend Snippet: Principal component analysis (PCA) of the cytokine profiles in the supernatants of splenocyte cultures stimulated in vitro with LiAg. (A) Noninfected mice. (B) Noninfected mice were treated with 6 mg/kg/day memantine. (C) Infected untreated mice. (D) Infected mice were treated with 6 mg/kg/day memantine. The direction and length of a vector indicate how a cytokine or immune mediator contributes to the two principal components in the plot. PC1 separates regulatory (IL-10-driven) from effector Th1/Th17-associated responses, whereas PC2 reflects differences in the coordination and intensity of cytokine activation. PL, parasite load; NO, nitric oxide.

Article Snippet: Memantine hydrochloride was obtained from Tocris Bioscience (Bristol, UK).

Techniques: In Vitro, Infection, Plasmid Preparation, Activation Assay