This graphic shows the pharmacological activity of the atypical antipsychotics. Olanzapine and quetiapine have affinity for histaminergic, adrenergic, serotoninergic and dopaminergic receptors. The receptor affinity profile of clozapine is used as the representative of this class of agents. Clozapine is a D2 and 5HT2A receptor antagonist that is used in treatment resistant schizophrenics. Many of the atypical antipsychotics were developed to take advantage of the serotonergic receptor heterogeneity seen throughout the dopaminergic system.
By blocking the presynaptic 5HT2A receptors present in the nigrostriatal and mesocortical tracts, the net effect of a decrease in dopamine neurotransmission was reduced. The associated side effects seen with chronic antipsychotic therapy in these tracts were reduced. When atypical antipsychotics such as risperidone are used, patients suffer less from extrapyramidal and cognitive side effects. However, clozapine does block many other receptors, causing significant side effects.
Due to the selective D2 antagonism in the mesolimbic system, atypical antipsychotics are also useful in bipolar disorders.
Extra info: The pathophysiology of bipolar disorder is largely in the limbic areas. Therefore D2 selectivity in this region is desirable.
Selectivity of risperidone for the 5-HT2A receptor over the D2 receptor seems to be dose dependent.
Extra info: Risperidone is also an atypical antipsychotic like clozapine. However, it seems to lose its preference for the 5HT2A receptor with increasing doses, therefore producing extrapyramidal side effects.
Atypical antipsychotics are more effective in treating psychosis than that of the low or high potency antipsychotics.
Extra info: To date, no large study has found one antipsychotic agent to be better than another when it comes to treating psychotic symptoms. Many claims have been made regarding better tolerability (i.e. less side effects, fewer doses, etc.)