Neuropharmacology of second-generation antipsychotic drugs: a validity of the serotonin-dopamine hypothesis.

Newer atypical antipsychotic drugs such as risperidone, olanzapine, quetiapine, ziprasidone and aripiprazole that have been modelled on the prototype agent clozapine and developed since the 1990 s are now referred to as second-generation antipsychotic drugs (SGAs). It has been proposed that the interaction between serotonin (5-HT) and dopamine systems may play a critical role in the mechanism of action of atypical antipsychotic drugs because a relatively potent blockade of 5-HT(2A) receptors coupled with the weaker antagonism of the dopamine D(2) receptors is found to be the only pharmacological feature which most atypical antipsychotic drugs have in common. This so-called 'serotonin-dopamine hypothesis' has become a useful model for developing new SGAs to achieve superior antipsychotic efficacy with a lower incidence of extrapyramidal side effects compared to those with first-generation antipsychotic drugs (FGAs) such as haloperidol and chlorpromazine, although it has not been validated yet.