Which properties make a neuroleptic "atypical"?

The group of "atypical" neuroleptics is not a homogeneous class of drugs, but pharmacologically as well as clinically disparate. Furthermore, there seems to be a continuum between "conventional" and "atypical" neuroleptics. Based on preclinical findings with these drugs and their characteristics in SPECT- and PET-studies, the most common concepts of neuroleptic "atypicality" are discussed. Combined D2-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 substances, affinities for specific neurotransmitter receptors as well as interactions with other non-dopaminergic systems may be essential. A relatively low affinity for D2-like dopamine receptors and binding to dopamine autoreceptors are probably of some importance for other compounds. The diversity of possible mechanisms suggests that there is not a single, pharmacologically established concept of "atypicality". A variety of biological mechanisms characterizes a heterogeneous group of substances, which also substantially differ in their clinical properties.