Putative hormetic mechanisms and effects of atypical antipsychotic agents: Implications for study design and clinical psychopharmacotherapeutics

This paper addresses a novel putative mechanism by which atypical antipsychotic agents induce clinically significant neuroprotective effects that may be viable in the treatment of schizophrenia – and perhaps other neuropsychiatric disorders. Based upon experimental studies with multiple in vitro models (i.e., PC 12 cells, NSC-34 hybrid cells, SH-SY5Y cells, the immune cell line U-937) and several rodent in vivo models, six atypical antipsychotic drugs, within direct experimental comparisons and/or preconditioning protocol studies with six different stressor/toxic agents (i.e. rotenone, hydrogen peroxide, MPP+, serum withdrawal, beta-amyloid, and corticosterone) were demonstrated to induce neuroprotective effects with consistently hormetic dose response patterns. These findings suggest that some of the reported neuroprotective effects of atypical human antipsychotic agents are likely to be mediated by hormetic mechanisms. These findings may have important implications for both experimental study design and clinical therapeutics.