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Annals of General Psychiatry

Open AccessOral presentationThe pharmacology and mechanisms of action of atypical antipsychotic drugs: dopamine and beyondDavid Sanger*

Address: Sanofi-Aventis Research, Bagneux, France, European Editor, Behavioural Pharmacology

* Corresponding author

The essential defining feature of atypical antipsychoticdrugs is that they are efficacious against the symptoms ofschizophrenia but produce fewer motor side effects (EPS)than classical drugs. In addition, there is evidence thatatypical agents may be more effective than classical neu-roleptics in treatment resistant patients and patients withpredominantly negative symptoms. All currently usedantipsychotics, both typical and atypical, have affinity forthe D2 family of dopamine receptors, at which they act asantagonists. Nevertheless, because some atypical agents,including clozapine, also bind to receptors for other neu-rotransmitters, particularly serotonin, it has been pro-posed that such additional mechanisms may be ofparticular importance in producing an atypical pharmaco-logical profile. However, there is evidence that selectiveaction at dopaminergic mechanisms in certain brainregions can also give rise to antipsychotic efficacy with avery low risk of EPS. Although most atypical drugs haveaffinities for a variety of neurotransmitter receptors, twodrugs, amisulpride and aripiprazole, have been proposedas selective dopaminergic agents. Amisulpride is a selec-tive antagonist at dopamine D2 and D3 receptors whereasaripiprazole may act through partial agonism at D2 recep-tors. The good efficacy and safety of these drugs raise ques-tions about the roles of neurotransmitters other thandopamine. Nevertheless, a number of ongoing researchprogrammes are currently underway in the search for thenext generation of antipsychotics. While many of theseprogrammes target sites other than dopamine receptors(including receptors for glutamate and neuropeptides), itseems likely that indirect modulation of dopaminergicneurotransmission will play a major role in their mecha-nisms of action.

from International Society on Brain and Behaviour: 2nd International Congress on Brain and BehaviourThessaloniki, Greece. 17–20 November 2005

Published: 28 February 2006

Annals of General Psychiatry 2006, 5(Suppl 1):S34 doi:10.1186/1744-859X-5-S1-S34<supplement> <title> <p>International Society on Brain and Behaviour: 2nd International Congress on Brain and Behaviour</p> </title> <note>Meeting abstracts – A single PDF containing all abstracts in this Supplement is available <a href="http://www.biomedcen-tral.com/content/files/pdf/1744-859X-5-S1-full.pdf">here</a>.</note> </supplement>