Partial Dopamine D2/Serotonin 5-HT1A Receptor Agonists as New Therapeutic Agents~!2009-12-17~!2010-04-07~!2010-07-20~!

Abstract

The therapeutic efficacy of current antipsychotic or antidepressant agents still present important drawbacks such as delayed onset of action and a high percentage of non-responders. Despite significant advancements in the devel- opment of new drugs with more acceptable side-effect profiles, patients with schizophrenia or major depression experi- ence substantial disability and burden of disease. The present review discusses the usefulness of partial dopamine D2/serotonin 5-HT1A receptors agonists in the treatment of schizophrenia, major depression and bipolar disorder as well as in Parkinson's disease. Partial agonists can behave as modulators since their intrinsic activity or efficacy of a partial ago- nist depends on the target receptor population and the local concentrations of the natural neurotransmitter. Thus, these drugs may restore adequate neurotransmission while inducing less side effects. In schizophrenia, partial DA D2/5-HT1A receptor agonists (like aripiprazole or bifeprunox), by stabilizing DA system via a preferential reduction of phasic DA re- lease, reduce side effects i.e. extrapyramidal symptoms and improve cognition by acting on 5-HT1A receptors. Aripipra- zole appears also as a promising agent for the treatment of depression since it potentiates the effect of SSRIs in resistant treatment depression. Concerning bipolar disorders aripiprazole may have only a benefit effect in the treatment of manic episodes. Conversely, treatment of Parkinson's disease with partial DA D2/5-HT1A receptor agonists remains still experi- mental. However several studies suggest that these drugs decrease usually observed side effects (dyskinesia, psychotic- like symptoms) in Parkinson's disease treatment. Hence, these relatively recent researches provide an exciting future in the discovery of novel stabilizators agents for the management of the latter diseases.