Adell Albert
Instituto de Investigaciones Biomédicas de Barcelona, Consejo Superior de Investigaciones Científicas, and Centro de Investigación Biomédica en Red de Salud Mental, Department of Neurochemistry and Neuropharmacology, Carrer Rosselló 161, Barcelona 08036, Spain.
IDrugs. 2010 Dec;13(12):900-10.
Lu-AA21004, an oral, multimodal serotonergic agent, is currently under development by H Lundbeck and Takeda Pharmaceutical, for the potential treatment of depression and anxiety. Lu-AA21004 belongs to a novel chemical class of antidepressant agents, the bisarylsulfanyl amines, and possesses a novel pharmacological profile, with activity at serotonergic receptors 5-HT3, 5-HT7 and 5-HT1A, and also at the 5-HT transporter. Acute administration of Lu-AA21004 in rats inhibited the firing activity of serotonergic neurons of the dorsal raphe nucleus through 5-HT3 receptor blockade, with rapid recovery of firing activity upon cessation of treatment compared with an antidepressant of the SSRI class. Results from phase II clinical trials have reported improvement in depression and anxiety symptoms after 6 weeks of treatment. Lu-AA21004 was generally well tolerated, with adverse events related to sexual dysfunction occurring in a lower number of patients receiving Lu-AA21004 compared with venlafaxine. Phase III clinical trials with Lu-AA21004 in patients with major depressive disorder are underway and phase III trials in patients with generalized anxiety disorder have been completed. If initial outcomes from these clinical trials prove positive, Lu-AA21004 may pave the way for new multimodal therapies for the treatment of depression and anxiety.
鲁-AA21004是一种口服多模式血清素能药物，目前由H.伦德贝克公司和武田制药公司进行研发，用于潜在治疗抑郁症和焦虑症。鲁-AA21004属于一类新型抗抑郁化学药物——双芳基硫烷基胺，具有新型药理学特征，对血清素能受体5-HT3、5-HT7和5-HT1A以及5-羟色胺转运体均有活性。在大鼠中急性给予鲁-AA21004，通过阻断5-HT3受体抑制中缝背核血清素能神经元的放电活动，与选择性5-羟色胺再摄取抑制剂（SSRI）类抗抑郁药相比，停药后放电活动能迅速恢复。II期临床试验结果报告称，治疗6周后抑郁症和焦虑症症状有所改善。鲁-AA21004总体耐受性良好，与文拉法辛相比，接受鲁-AA21004治疗的患者中发生性功能障碍相关不良事件的人数较少。针对重度抑郁症患者的鲁-AA21004 III期临床试验正在进行中，针对广泛性焦虑症患者的III期试验已经完成。如果这些临床试验的初步结果证明是积极的，鲁-AA21004可能为抑郁症和焦虑症的新型多模式治疗铺平道路。
