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In the 1950s antipsychotic antidopaminergic drugs were introduced as the pharmacological treatment of schizophrenia. In the last 35 years a large fund of knowledge has been acquired about these drugs. Still, a number of issues regarding them require further addressing. We have reviewed the literature on some of these issues, focusing on those factors that the previous studies have resolved inadequately. The issue of optimal dosages of antipsychotics in schizophrenia has been analyzed from the perspective of the dose requirements during "rapid tranquilization", "in acute psychotic phases of schizophrenia", "in chronically hospitalized psychotic schizophrenic patients" and during "maintenance phases of schizophrenia". We have briefly discussed the different methodologies available for measuring neuroleptic levels in plasma, their methodological weaknesses and strengths and some of the larger studies done with chlorpromazine, haloperidol and fluphenazine to establish correlations between levels, treatment response, oral dosages and side-effects. The theoretically fascinating concept of supersensitivity psychosis has been reviewed and the theoretical and practical weaknesses that exist in most of the papers that have claimed validity for this concept are presented. The article also reviews the preclinical, postmortem and clinical research that demonstrates the presence of site selectivity for dopamine receptors in the newer atypical neuroleptics. Finally, the article briefly reviews the current status of some unorthodox clinical strategies, that may be potentially applicable in managing schizophrenic disorders.

The antipsychotic efficacy of tiaspirone, a new atypical antipsychotic agent, was compared to standard neuroleptics, in a single-blind cross-over study. Nine actively psychotic schizophrenic patients entered the study and 6 completed it. Significant overall improvement, on BPRS and CGI ratings, occurred by week 4, on both--tiaspirone and standard neuroleptics. There were no significant differences between tiaspirone and standard neuroleptics, in their antipsychotic efficacy. In keeping with the preclinical profile of tiaspirone, no extrapyramidal symptoms (EPS) were observed with tiaspirone. Two patients showed EPS on standard neuroleptics. Five of the 6 patients showed mild transient elevation of liver enzymes while on tiaspirone. Liver enzymes returned to normal within 3 weeks of discontinuation of tiaspirone. Tiaspirone appears to be a promising new antipsychotic agent that may be clinically effective without causing extrapyramidal syndromes.