Brink Christiaan B, Harvey Brian H, Brand Linda
Division of Pharmacology, North-West University (PUK), Potchefstroom, 2520, South Africa.
Recent Pat CNS Drug Discov. 2006 Jan;1(1):29-41. doi: 10.2174/157488906775245327.
Tianeptine, an atypical antidepressant patented and developed by Servier, enhances the synaptic reuptake of serotonin, without affecting norepinephrine and dopamine uptake, while it lacks affinity for neurotransmitter receptors. This mechanism for an antidepressant is apparently paradoxical, since the currently employed antidepressants enhance serotonin by inhibiting its breakdown or by inhibiting monoaminergic reuptake. Although tianeptine has been shown to reduce central 5HT availability and to indirecty modulate central adrenergic and dopaminergic systems and to indirectly inhibit cholinergic hyperactivity, its antidepressant action is believed to be more directly related to central neuronal remodeling and restoration of neuronal plasticity. In reliable animal models of depression tianeptine has been shown to prevent neurodegeneration and decreases in hippocampal volume in response to chronic stress. These effects on neuroplasticity are suspected to involve the normalization of the hypothalamic-pituitary-adrenal axis and modulatory effects on excitatory amino acids and N-methyl-D-aspartate receptors. Together with a body of related studies, these data provide further support for the hypothesis that depression may involve dysregulation of pathways controlling cellular resilience and that treatment should be directed towards the reversal thereof. Importantly, tianeptine is not anxiogenic and has also been shown to be effective in treatment-resistant depression, which may lead the way to a major breakthrough in the treatment of depression.
噻奈普汀是施维雅公司获得专利并研发的一种非典型抗抑郁药，它可增强5-羟色胺的突触再摄取，而不影响去甲肾上腺素和多巴胺的摄取，同时它对神经递质受体缺乏亲和力。这种抗抑郁药的作用机制显然自相矛盾，因为目前使用的抗抑郁药是通过抑制5-羟色胺的分解或抑制单胺能再摄取来增强其作用的。尽管已表明噻奈普汀可降低中枢5-羟色胺的可用性，并间接调节中枢肾上腺素能和多巴胺能系统，间接抑制胆碱能功能亢进，但其抗抑郁作用被认为更直接地与中枢神经元重塑和神经元可塑性的恢复有关。在可靠的抑郁症动物模型中，噻奈普汀已被证明可预防神经变性，并防止因慢性应激导致的海马体体积减小。这些对神经可塑性的影响被怀疑涉及下丘脑-垂体-肾上腺轴的正常化以及对兴奋性氨基酸和N-甲基-D-天冬氨酸受体的调节作用。连同一系列相关研究，这些数据为抑郁症可能涉及控制细胞复原力的通路失调以及治疗应针对逆转这种失调的假说提供了进一步支持。重要的是，噻奈普汀不会引发焦虑，并且已被证明对难治性抑郁症有效，这可能为抑郁症的治疗带来重大突破。
