Therapeutic potential of serotonin antagonists in depressive disorders.
Although the precise neurochemical imbalances in depression are still unknown, a role for the neurotransmitter 5-hydroxytryptamine (serotonin) has been implicated since the identification of the first effective antidepressants, imipramine and iproniazid. This led to the development of the selective serotonin re-uptake inhibitors which are widely used in the treatment of depression and depressive disorders, including generalised anxiety disorder, social phobia, obsessive compulsive disorder etc. Studies involving chronic administration in rats led to the hypothesis that the different classes of antidepressant treatment produce a common neuroadaptive change, namely an enhancement of serotonin neurotransmission, albeit via different pre and postsynaptic mechanisms. From this, it was suggested that serotonin antagonists should induce similar neuroadaptive changes, either directly or through a potentiation of other antidepressant agents. Here, the profiles of novel serotonin antagonists currently in preclinical development are reviewed and their therapeutic potential is assessed.
Wood
Martyn D
MD
Psychiatry Centre for Excellence in Drug Discovery, GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow, Essex, CM19 5AW, UK. Martyn_Wood-1@gsk.com
Thomas
David R
DR
Watson
Jeannette M
JM
D000818:Animals; D003866:Depressive Disorder / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D009771:Obsessive-Compulsive Disorder / Q000188:drug therapy* / Q000503:physiopathology; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012702:Serotonin Antagonists / Q000627:therapeutic use*; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use
D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors