Building a better antipsychotic: receptor targets for the treatment of multiple symptom dimensions of schizophrenia.
Attempts to develop selective ("magic bullet") drugs for the treatment of schizophrenia have been frustrated by the complex etiology of the disease. The symptomatology of schizophrenia does not appear to arise from a single neurobiological entity, but rather may be derived from pathology at one or more receptor types. This has prompted multifactorial approaches to the development of new therapeutics, as embodied by polypharmacy and an alternative (or augmentative) strategy known as "intramolecular polypharmacy," in which a single drug possesses the capacity to affect multiple receptor types. Atypical antipsychotics are a well-known example of this approach; each atypical possesses a unique portfolio of activities at receptors that may contribute to therapeutic effects (as well as side effects). In this article we present a discussion of some of the receptor targets that are currently thought to mediate symptoms of schizophrenia, as well as their possible implications for the design of future multifunctional antipsychotics.
Kim
Dennis H
DH
Arbor Scientia, Carlsbad, California 92008, USA.
Maneen
Matthew J
MJ
Stahl
Stephen M
SM
D000818:Animals; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D004298:Dopamine / Q000378:metabolism; D065127:Dopamine D2 Receptor Antagonists; D016503:Drug Delivery Systems; D015195:Drug Design; D018684:Glycine Agents / Q000627:therapeutic use; D006801:Humans; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000378:metabolism; D017470:Receptors, Glutamate / Q000378:metabolism; D011985:Receptors, Serotonin / Q000378:metabolism; D012559:Schizophrenia / Q000188:drug therapy*; D012702:Serotonin Antagonists / Q000627:therapeutic use; D017366:Serotonin Receptor Agonists / Q000627:therapeutic use
D014150:Antipsychotic Agents; D065127:Dopamine D2 Receptor Antagonists; D018684:Glycine Agents; D017448:Receptors, Dopamine D2; D017470:Receptors, Glutamate; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D004298:Dopamine