Briley M, Prost J F, Moret C
Centre de Recherche Pierre Fabre, Castres, France.
Int Clin Psychopharmacol. 1996 Sep;11 Suppl 4:9-14. doi: 10.1097/00004850-199609004-00002.
Milnacipran (Ixel) is a new antidepressant which has been developed for its selective inhibition of both serotonin and noradrenaline reuptake and its lack of affinity for neurotransmitter receptors. It inhibits virtually equipotently the reuptake of serotonin and noradrenaline both in vitro and in vivo, as demonstrated by the antagonism of centrally acting monoamine displacers. It has no effect on dopamine reuptake. In addition, milnacipran has been shown by intracerebral microdialysis to increase the extracellular levels of both serotonin and noradrenaline after acute administration. Milnacipran is devoid of interactions at any known neurotransmitter receptor or ion channel. In particular, and unlike tricyclic antidepressants, it does not act at noradrenergic, muscarinic or histaminergic receptors. Contrary to tricyclic antidepressants, chronic administration of milnacipran does not modify beta-adrenoceptor binding or second messenger function. Milnacipran is active on various animal models of depression such as the forced swimming test in the mouse, learned helplessness in the rat and the olfactory bulbectomized rat model. This pharmacological profile, associated with an excellent bioavailability in man, was predicted to be that required for a powerful and well-tolerated antidepressant. Subsequent clinical development has shown this prediction to be well founded.
米那普明（喜普妙）是一种新型抗抑郁药，其研发目的在于选择性抑制5-羟色胺和去甲肾上腺素的再摄取，且对神经递质受体缺乏亲和力。正如中枢作用单胺置换剂的拮抗作用所表明的那样，它在体外和体内对5-羟色胺和去甲肾上腺素再摄取的抑制作用几乎相当。它对多巴胺再摄取没有影响。此外，脑内微透析显示，急性给药后米那普明可提高5-羟色胺和去甲肾上腺素的细胞外水平。米那普明在任何已知的神经递质受体或离子通道上均无相互作用。特别是，与三环类抗抑郁药不同，它不作用于去甲肾上腺素能、毒蕈碱能或组胺能受体。与三环类抗抑郁药相反，长期服用米那普明不会改变β-肾上腺素受体结合或第二信使功能。米那普明在多种抑郁动物模型上均有活性，如小鼠强迫游泳试验、大鼠习得性无助模型和嗅球切除大鼠模型。这种药理学特性，再加上在人体中出色的生物利用度，预计是一种强效且耐受性良好的抗抑郁药所必需的。后续的临床研究表明这一预测是有充分依据的。
