Which Atypical Antipsychotics Are Identified by Screening Tests?

Only two tests were specific for antipsychotic potential. All effective antipsychotics blocked pharmacologically induced locomotion and affected firing in the mesolimbic DA neurons. The remaining single- (Table 1) and repeated- (Table 2) dose tests identified the atypical antipsychotics. Clozapine, thioridazine, sulpiride, tiospirone, and molindone were atypical in both types of study. Pimozide, pipamperone, aceperon, methylperon, and clotiapine were atypical in single-dose studies, clopenthixol in repeated-dose studies. Since the biochemical abnormality causing psychoses is unknown, it may be that current methods of screening for new antipsychotics are inadequate and possibly inappropriate. If a neurotransmitter other than DA is the primary cause, then totally new tests may be needed. Present tests, especially those involving behavioral paradigms, may continue to select out compounds that cause EPS side-effects. New methods such as positron emission tomography scanning and other brain-imaging techniques hold the promise of studying specific types and subtypes of receptors in the living human brain. The recent discovery of chromosomal abnormalities in psychotic illness may provide new insights into the biochemical causes of such disorders and lead to completely new compounds that will be both safer and more effective. In the meantime we plan to review the literature on the clinical use of the compounds identified as atypical in this article and to develop research protocols to assess their efficacy in treatment-resistant psychoses and intractable conditions such as tardive dyskinesia.