Preclinical pharmacology of TP1, a novel potent triple reuptake inhibitor with antidepressant properties

Tian, Jingwei; Jiang, Wanglin; Zhong, Yan; Meng, Qingguo; Gai, Yunyun; Zhu, Haibo; Hou, Jian; Xing, Yanli; Li, Y.-X.

doi:10.1016/j.neuroscience.2011.08.064

Cited by 16 publications

(20 citation statements)

References 18 publications

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“…Similarly, antidepressants known as norepinephrine reuptake inhibitors (NRIs) have been used to target the norepinephrine transporter (NET). This strategy can also be used in conjunction with those targeting SERT (thus, serotonin-norepinephrine reuptake inhibitors, SNRIs) and those targeting the dopamine transporter (DAT) 11. Nevertheless, evidence supporting monoamine signaling as the direct precipitating factor in depressive pathogenesis is lacking.…”

Section: The Molecular Pathophysiology Of Depressionmentioning

confidence: 99%

MicroRNA as therapeutic targets for treatment of depression

Hansen¹,

Obrietan²

2013

NDT

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Depression is a potentially life-threatening mental disorder affecting approximately 300 million people worldwide. Despite much effort, the molecular underpinnings of clinical depression remain poorly defined, and current treatments carry limited therapeutic efficacy and potentially burdensome side effects. Recently, small noncoding RNA molecules known as microRNA (miRNA) have gained prominence as a target for therapeutic intervention, given their capacity to regulate neuronal physiology. Further, mounting evidence suggests a prominent role for miRNA in depressive molecular signaling. Recent studies have demonstrated that dysregulation of miRNA expression occurs in animal models of depression, and in the post-mortem tissue of clinically depressed patients. Investigations into depression-associated miRNA disruption reveals dramatic effects on downstream targets, many of which are thought to contribute to depressive symptoms. Furthermore, selective serotonin reuptake inhibitors, as well as other antidepressant drugs, have the capacity to reverse aberrant depressive miRNA expression and their downstream targets. Given the powerful effects that miRNA have on the central nervous system transcriptome, and the aforementioned studies, there is a compelling rationale to begin to assess the potential contribution of miRNA to depressive etiology. Here, we review the molecular biology of miRNA, our current understanding of miRNA in relation to clinical depression, and the utility of targeting miRNA for antidepressant treatment.

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Section: The Molecular Pathophysiology Of Depressionmentioning

confidence: 99%

MicroRNA as therapeutic targets for treatment of depression

Hansen¹,

Obrietan²

2013

NDT

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“…The protocol to determine locomotor activity was adapted from a previously published method28. Briefly, the animals were individually placed in a custom-fabricated activity box (35 × 30 × 22 cm).…”

Section: Methodsmentioning

confidence: 99%

Antidepressant-like activity of adhyperforin, a novel constituent of Hypericum perforatum L.

Tian

Zhang

Cheng

et al. 2014

Sci Rep

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Adhyperforin is a novel constituent of Hypericum perforatum L., but its antidepressant-like activity remains unclear. To explore that, several well-validated animal models of depression as well as neurotransmitter reuptake and transporter binding assays were conducted. The results showed adhyperforin could reduce the immobility time of mice in the forced swimming test and tail suspension assay, antagonize the behaviors induced by reserpine, and have no effect on locomotor activity. Furthermore, following establishment of a chronic unpredictable mild stress model, adhyperforin increased the number of crossings and rearings in rats in the open field test and increased the sucrose consumption. Finally, adhyperforin inhibited uptake of serotonin, norepinephrine, and dopamine, and displayed robust binding affinities for the serotonin and norepinephrine transporters. Overall, the current study provides the first evidence that adhyperforin is a novel, active ingredient of Hypericum perforatum L. with robust antidepressant-like activity.

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“…Since DA is known to enhance locomotor activity, the possibility cannot be excluded that TRIs increased the time of immobility in these various studies, through a psychostimulant effect. In various studies, however, TRIs did not modify locomotor activity at doses that produce antidepressant-like effects (Tian et al, 2011;Aluisio et al, 2008;Liang et al, 2008;Shaw et al, 2007;Skolnick et al, 2003), thereby ruling out the possibility that the antidepressant-like activity detected does not appear to be from "falsepositive" results. An important drawback in the development of antidepressants is the fact that the new compounds are tested after acute administration in naïve, non-depressed animals.…”

Section: Behavioral Effects Of Trismentioning

confidence: 96%