The role of dopamine and norepinephrine in depression and antidepressant treatment.
Most antidepressants in use today are descendants of the monoamine oxidase inhibitor iproniazid and the tricyclic agent imipramine. These agents were both originally developed for other indications but then were serendipitously determined to have antidepressant effects. Elucidation of the mechanisms of action of these first antidepressants, along with those of reserpine and amphetamine, led to the monoamine theories of depression. Through the past several decades, approaches undertaken to clarify the roles of the neurotransmitters norepinephrine, dopamine, and serotonin in depression have included animal studies, human biological and postmortem studies, inferences drawn from antidepressant drug actions, and challenge or depletion studies; most recently, brain imaging studies have proved to be especially informative. This research has identified novel potential targets, with the goal of developing new antidepressant drugs with better efficacy and faster onset of action than current "gold-standard" treatments.
Nutt
David J
DJ
Psychopharmacology Unit, School of Medical Sciences, University of Bristol, Bristol, UK. david.j.nutt@bristol.ac.uk
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D003866:Depressive Disorder / Q000188:drug therapy* / Q000503:physiopathology*; D004298:Dopamine / Q000502:physiology*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000187:drug effects / Q000378:metabolism; D015195:Drug Design; D006801:Humans; D018377:Neurotransmitter Agents / Q000502:physiology; D009638:Norepinephrine / Q000502:physiology*; D049268:Positron-Emission Tomography; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism; D012701:Serotonin / Q000502:physiology; D015899:Tomography, Emission-Computed, Single-Photon
D000928:Antidepressive Agents; D050483:Dopamine Plasma Membrane Transport Proteins; D018377:Neurotransmitter Agents; D011954:Receptors, Dopamine; D012701:Serotonin; D004298:Dopamine; D009638:Norepinephrine