Which properties make a neuroleptic "atypical"?

The group of "atypical" neuroleptics is not a homogeneous class of drugs, b ut pharmacologically as well as clinically disparate. Furthermore, there se ems to be a continuum between "conventional" and "atypical" neuroleptics. B ased on preclinical findings with these drugs and their characteristics in SPECT-and PET-studies, the most common concepts of neuroleptic "atypicality " are discussed. Combined D-2-like dopamine/5-HT2-serotonin antagonism and preferential binding to mesolimbic dopamine neurons are believed to be the main pharmacological features of "atypical" compounds. For certain substanc es, affinities for specific neurotransmitter receptors as well as interacti ons with other non-dopaminergic systems may be essential. A relatively low affinity for D2-like dopamine receptors and binding to dopamine autorecepto rs are probably of some importance for other compounds. The diversity of po ssible mechanisms suggests that there is not a single, pharmacologically es tablished concept of "atypicality". A variety of biological mechanisms char acterizes a heterogeneous group of substances, which also substantially dif fer in their clinical properties.