Antipsychotic drug development

Schizophrenia typically manifests itself with a wide array of symptoms--positive, negative, cognitive, and affective--and may also involve neurodevelopmental and neurodegenerative aspects. Each of these symptom dimensions may be derived from pathology at one or more receptor types, localized in different regions of the brain. The absence of a single therapeutic target for schizophrenia has therefore prompted the de-emphasis of selective "magic bullets" and a critical re-examination of the intramolecular polypharmacy afforded by antipsychotics. In this chapter, we present a review of some of the receptor targets that are currently thought to mediate symptoms of schizophrenia, and discuss their possible implications for future antipsychotic drug development. Therapeutic strategies for schizophrenia that successfully exploit the multifunctionality of antipsychotics will take into account the entire receptor activity "portfolio" of the agent and provide a total therapeutic response that, like the elephant of the Buddhist parable, is greater than the sum of its parts.