Discriminative stimulus properties of antipsychotics.

Drug discrimination methodology has been used in a number of ways to analyze the actions of novel and putative novel antipsychotics in vivo. Recent studies suggest (a) in contrast to earlier theorizing, antagonism of the low-dose d-amphetamine stimulus in rats may not be an effective screen for novel antipsychotics; (b) dopamine D2-like agonists and antagonists, some of which are putative antipsychotics, can be studied in vivo as discriminative cues, although there is a pressing need for more selective drugs that differentiate the various members of the D2 family. (c) antagonism of the cue induced by the noncompetitive NMDA antagonist MK-801, which has been proposed as a possible screen for clozapine-like compounds, may be an unreliable assay; and (d) the clozapine stimulus is probably a compound cue (a drug "mixture"), which can be used to screen for novel clozapine-like antipsychotics, although the precise receptor mechanisms involved in mediating the clozapine stimulus, and its direct relevance to the antipsychotic action of clozapine remains to be proven conclusively.