5-HT2 ligands in the treatment of anxiety and depression.
BACKGROUND
One third of depressed patients do not respond adequately to conventional antidepressants including the selective serotonin reuptake inhibitors (SSRIs). Therefore, multi-target drugs or augmentation strategies have been developed for the management of SSRIs-resistant patients. In this context, the 5-HT(2) receptor subtypes represent promising targets but their precise roles have yet to be determined.


METHODS
The aim of this review is to shed some light on the preclinical evidence supporting the use of 5-HT(2A) and/or 5-HT(2C) receptor antagonists such as antipsychotics, as potential effective adjuncts in SSRIs-resistant depression. This review synthesizes the current literature about the behavioral, electrophysiological and neurochemical effects of 5-HT(2) receptors ligands on the monoaminergic systems but also on adult hippocampal neurogenesis.


CONCLUSIONS
Although studies support the hypothesis that the inactivation of 5-HT(2A) and/or 5-HT(2C) receptors might be of interest to reinforce different facets of the therapeutic activity of SSRIs, this pharmacological strategy remains debatable notably because of the lack of chronic data in relevant animal models. Conversely, emerging evidence suggests that the activation of 5-HT(2B) receptor is required for antidepressant-like activity, opening the way to new therapeutic approaches. However, the potential risks related to the enhancement of monoaminergic neurotransmissions could represent a major concern.
EA3544 University Paris-XI, Laboratoire de Neuropharmacologie, Fac. Pharmacie, F-92296, Châtenay-Malabry cedex, France.
Gaël
G
Quesseveur
Hai T
HT
Nguyen
Alain M
AM
Gardier
Bruno P
BP
Guiard
D000328:Adult; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology / Q000627:therapeutic use; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D001008:Anxiety Disorders / Q000188:drug therapy / Q000503:physiopathology; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D003866:Depressive Disorder / Q000188:drug therapy / Q000503:physiopathology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D055495:Neurogenesis / Q000187:drug effects; D044348:Receptors, Serotonin, 5-HT2 / Q000187:drug effects* / Q000378:metabolism; D058826:Serotonin 5-HT2 Receptor Agonists / Q000494:pharmacology / Q000627:therapeutic use*; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use*
D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D044348:Receptors, Serotonin, 5-HT2; D058826:Serotonin 5-HT2 Receptor Agonists; D058830:Serotonin 5-HT2 Receptor Antagonists