New approaches to antidepressant drug discovery: beyond monoamines.
All available antidepressant medications are based on serendipitous discoveries of the clinical efficacy of two classes of antidepressants more than 50 years ago. These tricyclic and monoamine oxidase inhibitor antidepressants were subsequently found to promote serotonin or noradrenaline function in the brain. Newer agents are more specific but have the same core mechanisms of action in promoting these monoamine neurotransmitters. This is unfortunate, because only approximately 50% of individuals with depression show full remission in response to these mechanisms. This review summarizes the obstacles that have hindered the development of non-monoamine-based antidepressants, and provides a progress report on some of the most promising current strategies.
Berton
Olivier
O
Department of Psychiatry and Center for Basic Neuroscience, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390-9070, USA.
Nestler
Eric J
EJ
D000818:Animals; D000928:Antidepressive Agents / Q000145:classification / Q000494:pharmacology / Q000627:therapeutic use*; D015306:Biogenic Monoamines; D001923:Brain Chemistry / Q000187:drug effects; D003866:Depressive Disorder / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000378:metabolism; D008959:Models, Neurological
D000928:Antidepressive Agents; D015306:Biogenic Monoamines