Lôo H, Deniker P
Service Hospitalo-Universitaire de Santé Mentale et de Thérapeutique, Hôpital Sainte Anne, Paris, France.
Clin Neuropharmacol. 1988;11 Suppl 2:S97-102.
The advent of a new antidepressant is always received with both interest and scepticism by clinicians. No new compound has yet been shown to be more efficient than imipramine in the treatment of depression. In determining the position of a compound among the antidepressants, four levels are to be considered: (a) Chemical family: Tianeptine is a tricyclic compound of dibenzothiazepine type. It is the only representative of this subgroup. (b) Biochemical activities: Tianeptine increases the presynaptic uptake of serotonin after single as well as repeated administration; but this action is not linked to any effect on the 5-HT post-synaptic systems. Electrophysiological modifications are observed in the locus coeruleus (noradrenergic) at 2.5 times higher doses; nevertheless, the essential action involves the serotoninergic systems. Tianeptine has no affinity for alpha 1 adrenergic and H1 antihistaminic receptors; this affinity is responsible in a large part for the sedative anxiolytic properties of antidepressants. Tianeptine has no affinity for the muscarinic receptors. It has secured its place among the non-anticholinergic antidepressants. The mechanism of action or the therapeutic profile cannot be inferred from this original biochemical profile. (c) In clinical trials, the double-blind trials confirm the antidepressant efficacy in essentially neurotic depressive syndromes, similar to that of imipramine, nomifensine, amitriptyline. They do not show a shorter onset time of antidepressant activity. The therapeutic profile appears to be neither stimulating nor sedative. Some arguments are in favor of an anxiolytic activity. Others favor a more psychotonic profile. Tianeptine can be classified among the mid-position antidepressants. (d) With respect to clinical acceptability, tianeptine has no anticholinergic effect and no cardiovascular effect.
临床医生对于新型抗抑郁药的问世总是既感兴趣又持怀疑态度。尚无新化合物在治疗抑郁症方面被证明比丙咪嗪更有效。在确定一种化合物在抗抑郁药中的地位时，需考虑四个层面：(a) 化学类别：噻奈普汀是二苯并硫氮杂䓬类三环化合物。它是该亚组的唯一代表。(b) 生化活性：单次及重复给药后，噻奈普汀均可增加5-羟色胺的突触前摄取；但此作用与对5-羟色胺突触后系统的任何效应均无关联。在剂量高出2.5倍时，可观察到蓝斑（去甲肾上腺素能）处的电生理改变；然而，其主要作用涉及5-羟色胺能系统。噻奈普汀对α1肾上腺素能受体和H1抗组胺受体无亲和力；这种亲和力在很大程度上导致了抗抑郁药的镇静抗焦虑特性。噻奈普汀对毒蕈碱受体无亲和力。它已在非抗胆碱能抗抑郁药中占据一席之地。无法从这一独特的生化特性推断其作用机制或治疗特点。(c) 在临床试验中，双盲试验证实其对本质上为神经症性抑郁综合征的抗抑郁疗效与丙咪嗪、诺米芬辛、阿米替林相似。它们并未显示出抗抑郁活性起效时间更短。治疗特点似乎既无兴奋作用也无镇静作用。一些证据支持其具有抗焦虑活性。另一些则支持其具有更强的精神振奋作用。噻奈普汀可归类于中等地位的抗抑郁药。(d) 在临床可接受性方面，噻奈普汀无抗胆碱能作用且无心血管作用。
