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Introduction: Due to severe burden of depressive disorders and a low rate of remission in patients receiving antidepressant therapy, there is an urgent need for developing novel agents with antidepressant action and a fundamentally new mechanism of action. 3-ethoxythietane-1,1-dioxide (N-199/1) is a new molecule that showed significant antidepressant properties when administered intraperitoneally once or repeatedly. The aim of the present study was to investigate the mechanism of action of N-199/1, using reserpine test. Materials and methods: N-199/1 (2 mg/kg and 4.86 mg/kg) and the reference drugs (imipramine and fluoxetine) were administered once intraperitoneally to outbred male mice 4 h (Experiment 1) and 18 h (Experiment 2) after a single intraperitoneal injection of reserpine (2.5 mg/kg). The severity of reserpine-induced symptoms (hypothermia, ptosis and akinesia) was assessed. Results and discussion: N-199/1 potentiated reserpine-induced hypothermia at both doses and reduced ptosis at a dose of 2 mg/kg when administered 4 h after reserpine. N-199/1 increased the duration of reserpine akinesia at a dose of 2 mg/kg when administered 18 h after reserpine and at a dose of 4.86 mg/kg when administered 4 h after reserpine. The effect of N-199/1 resembled the effect of fluoxetine and was dose-dependent. Conclusion: Based on the results obtained, it can be assumed that the antidepressant action of N-199/1 is due to its serotonin-positive properties, and probably the blockade of serotonin 5HT2A/2C receptors and/or α2-adrenergic receptors. The effect of N-199/1 is dose-dependent and resembles the effect of fluoxetine. Graphical abstract:

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The great diversity of nanomaterials provides ample opportunities for constructing effective agents for biomedical applications ranging from biosensing to drug delivery. Multifunctional nanoagents that combine several features in a single particle are of special interest due to capabilities that substantially exceed those of molecular drugs. An ideal theranostic agent should simultaneously be an advanced biosensor to identify a disease and report the diagnosis and a biomedical actuator to treat the disease. While many approaches were developed to load a nanoparticle with various drugs for actuation of the diseased cells (e.g., to kill them), the nanoparticle-based approaches for the localized biosensing with real-time reporting of the marker concentration severely lag behind. Here, we show a smart in situ nanoparticle-based biosensor/actuator system that dynamically and reversibly changes its structural and optical properties in response to a small molecule marker to allow real-time monitoring of the marker concentration and adjustment of the system ability to bind its biomedical target. Using the synergistic combination of signal readout based on the localized surface plasmon resonance and an original method of fabrication of smart ON/OFF-switchable nanoagents, we demonstrate reversible responsiveness of the system to a model small molecule marker (antibiotic chloramphenicol) in a wide concentration range. The proposed approach can be used for the development of advanced multifunctional nanoagents for theranostic applications.

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