Potential role of the 5-HT6 receptor in depression and anxiety: an overview of preclinical data.
Mental disorders, such as depression and anxiety, pose both medical and social challenges. The clinical efficacy of current antidepressant/anxiolytic therapies is unsatisfactory; both antidepressant and anxiolytic drugs induce a variety of unwanted effects and have delayed onsets of action. Thus, a search for better and safer agents is continuously in progress. Preclinical results published so far have brought new insights into the possible role of recently discovered serotonin 5-HT(6) receptors in these disorders. This review surveys the current state of knowledge regarding potential antidepressant and anxiolytic activities of selective 5-HT(6) receptor ligands, namely, full agonists and antagonists, in animal models commonly used to predict such activity. Evidence indicates that both 5-HT(6) agonists and antagonists may evoke identical responses in animal models of depression and anxiety; however, the possible mechanisms of these effects seem to be diverse and are not clearly understood. Especially interesting are the augmented effects achieved by combining antidepressants or diazepam with a selective 5-HT(6) receptor antagonist.
Wesołowska
Anna
A
Department of Clinical Pharmacy, Jagiellonian University Medical College, Medyczna 9, PL 30-688 Kraków, Poland. awesolowska@cm-uj.krakow.pl
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D000928:Antidepressive Agents / Q000494:pharmacology; D001007:Anxiety / Q000188:drug therapy* / Q000503:physiopathology; D003863:Depression / Q000188:drug therapy* / Q000503:physiopathology; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D006801:Humans; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C097216:serotonin 6 receptor