Norepinephrine and Schizophrenia: A New Hypothesis for Antipsychotic Drug Action

Abstract

Publisher Summary This chapter summarizes several researches to investigate many neurochemical effects of clozapine, an antipsychotic agent, for its superior clinical profile. This line of investigation is likely to lead to the development of even better agents for the treatment of schizophrenia. It has been found that neurochemical effect of clozapine is enhancement of noradrenergic activity. It is also found that clozapine produces fivefold increase in plasma norepinephrine (NE) levels, whereas traditional neuroleptics have essentially no effect on peripheral noradrenergic function. The chapter suggests that clozapine's effects on noradrenergic function are related to its superior clinical efficacy. To better understand the mechanism of clozapine's noradrenergic enhancement, a clinical study has been conducted in schizophrenic patients to assess effects on NE uptake, clearance, and spillover. It has been found that patients with schizophrenia had significantly higher arterially derived plasma NE levels than fluphenazine-treated and medication-free patients. The noradrenergic-enhancing property of clozapine raises questions about the role of NE in the pathophysiology of schizophrenia. It has been hypothesized that clozapine's superior clinical efficacy is related to its ability to enhance noradrenergic function that in turn improves synaptic strength in cortical regions responsible for the symptoms of this illness.