Journal
MOLECULAR PSYCHIATRY
Volume 13, Issue 10, Pages 918-929Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/mp.2008.40
Keywords
antipsychotic; functional selectivity; insulin; mechanism of action; metabolic side effects; schizophrenia
Funding
- NIH
- NATIONAL INSTITUTE OF MENTAL HEALTH [R01MH054137] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON DRUG ABUSE [K05DA022413] Funding Source: NIH RePORTER
Ask authors/readers for more resources
The exact therapeutic mechanism of action of antipsychotic drugs remains unclear. Recent evidence has shown that second-generation antipsychotic drugs (SGAs) are differentially associated with metabolic side effects compared to first-generation antipsychotic drugs (FGAs). Their proclivity to cause metabolic disturbances correlates, to some degree, with their comparative efficacy. This is particularly the case for clozapine and olanzapine. In addition, the insulin signaling pathway is vital for normal brain development and function. Abnormalities of this pathway have been found in persons with schizophrenia and antipsychotic drugs may ameliorate some of these alterations. This prompted us to hypothesize that the therapeutic antipsychotic and adverse metabolic effects of antipsychotic drugs might be related to a common pharmacologic mechanism. This article reviews insulin metabolism in the brain and related abnormalities associated with schizophrenia with the goals of gaining insight into antipsychotic drug effects and possibly also into the pathophysiology of schizophrenia. Finally, we speculate about one potential mechanism of action (that is, functional selectivity) that would be consistent with the data reviewed herein and make suggestions for the future investigation that is required before a therapeutic agent based on these data can be realized.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available