title: Lu-AA21004, a multimodal serotonergic agent, for the potential treatment of depression and anxiety.
abstract: 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.
authors.affiliation: 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. albert.adell@iibb.csic.es
authors.forename: Albert
authors.initials: A
authors.lastname: Adell
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D000928:Antidepressive Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D001008:Anxiety Disorders / Q000188:drug therapy*; D003865:Major Depressive Disorder / Q000188:drug therapy*; D015507:Drugs, Investigational / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D010879:Piperazines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*; D012702:Serotonin Antagonists / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*; D013440:Sulfides / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*; D000078784:Vortioxetine
chemical_list: D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D015507:Drugs, Investigational; D010879:Piperazines; D012702:Serotonin Antagonists; D013440:Sulfides; D000078784:Vortioxetine