MECHANISMS OF ACTION OF ATYPICAL ANTIPSYCHOTIC-DRUGS - A CRITICAL ANALYSIS

Various criteria used to define atypical antipsychotic drugs include: 1) decrease, or absence, of the capacity to cause acute extrapyramidal motor side effects (acute EPSE) and tardive dyskinesia (TD); 2) incre ased therapeutic efficacy reflected by improvement in positive, negati ve, or cognitive symptoms; 3) and a decrease, or absence. of the capac ity to increase prolactin levels. The pharmacologic basis of atypical antipsychotic drug activity has been the target of intensive study sin ce the significance of clozapine was first appreciated. Three notions have been utilized conceptually to explain the distinction between aty pical versus typical antipsychotic drugs: 1) dose-response separation between particular pharmacologic functions; 2) anatomic specificity of particular pharmacologic activities; 3) neurotransmitter receptor int eractions and pharmacodynamics. These conceptual bases are not mutuall y exclusive, and the demonstration of limbic versus extrapyramidal mot or functional selectivity is apparent within each arbitrary theoretica l base. This review discusses salient distinctions predominantly betwe en prototypic atypical and typical antipsychotic drugs such as clozapi ne and haloperidol, respectively. In addition, areas of common functio n between atypical and typical antipsychotic drug action may also be c rucial to our identification of pathophysiological foci of the differe nt dimensions of schizophrenia, including positive symptoms, negative symptoms, and neurocognitive deficits.