title: New approaches to developing antidepressants by enhancing monoaminergic neurotransmission.
abstract: Major depressive disorder (MDD) is a serious illness with far reaching societal and economic ramifications. The monoamine-deficiency hypothesis that depressive symptoms are associated with reductions in monoamine neurotransmission, particularly serotonin and noradrenaline, is supported by both neurochemical findings and the successful treatment of MDD with compounds that enhance monoaminergic neurotransmission. This review focuses on novel compounds in different stages of development for the treatment of MDD that enhance monoaminergic neurotransmission via a number of different mechanisms, including re-uptake inhibition of one or more monoamines, monoamine oxidase inhibitors, the combination of monoamine antagonists with re-uptake inhibitors and monoamine receptor subtype agonists. Compounds that enhance individual monoamines have antidepressant properties and compounds that enhance multiple monoamines appear to have a synergistic antidepressant effect and potentially faster onset of action. The differing mechanisms of action possessed by these novel monoamine-enhancing compounds will offer greater treatment flexibility in the therapeutic management of MDD.
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285-0510, USA. f.bymaster@lilly.com
authors.forename: Frank P
authors.initials: FP
authors.lastname: Bymaster
authors.forename: Robert K
authors.initials: RK
authors.lastname: McNamara
authors.forename: Pierre V
authors.initials: PV
authors.lastname: Tran
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000737:chemistry / Q000627:therapeutic use; D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use*; D015306:Biogenic Monoamines / Q000378:metabolism*; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000378:metabolism; D018491:Dopamine Agonists / Q000737:chemistry / Q000627:therapeutic use; D006801:Humans; D017366:Serotonin Receptor Agonists / Q000737:chemistry / Q000627:therapeutic use; D017367:Selective Serotonin Reuptake Inhibitors / Q000737:chemistry / Q000627:therapeutic use
chemical_list: D018759:Adrenergic Uptake Inhibitors; D000928:Antidepressive Agents; D015306:Biogenic Monoamines; D018491:Dopamine Agonists; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors