Skip Navigation



Schizophrenia Bulletin Advance Access published online on August 14, 2008
Schizophrenia Bulletin, doi:10.1093/schbul/sbn104
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Savoy, Y. E.
Right arrow Articles by Hajos-Korcsok, E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Savoy, Y. E.
Right arrow Articles by Hajos-Korcsok, E.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2008. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org.

Differential Effects of Various Typical and Atypical Antipsychotics on Plasma Glucose and Insulin Levels in the Mouse: Evidence for the Involvement of Sympathetic Regulation

Yvette E. Savoy2, Michael A. Ashton2, Matthew W. Miller2, Frank M. Nedza3, Douglas K. Spracklin3, Mark H. Hawthorn2, Hans Rollema4, F. Fatima Matos2 and Eva Hajos-Korcsok1,4
2 Department of General Pharmacology
3 Department of Pharmacokinetics, Dynamics and Metabolism
4 Department of Neuroscience, Pfizer Global Research and Development, Pfizer Inc, Eastern Point Road, Groton, CT 06340

1 To whom correspondence should be addressed; tel: 860-686-6879, fax: 860-686-0013, e-mail: eva.hajos-korcsok{at}pfizer.com.

Atypical antipsychotic treatment has been associated with serious metabolic adverse events, such as glucose dysregulation and development of type 2 diabetes. As part of our studies on possible underlying mechanisms, we investigated the acute effects of various typical and atypical antipsychotics on plasma glucose and insulin in FVB/N mice, a strain that showed a more pronounced hyperglycemic response to clozapine than C57BL/6 and CD-1 mice. Acute administration of high doses of clozapine, olanzapine, quetiapine, perphenazine, or chlorpromazine significantly increased plasma glucose by 100%–140% above basal levels without significant effects on insulin levels. In contrast, risperidone reduced plasma glucose (–30%) and markedly enhanced plasma insulin levels. Doses of ziprasidone that gave 50-fold higher free plasma concentrations than therapeutic plasma levels, as well as high doses of aripiprazole and haloperidol, did not significantly alter either glucose or insulin levels. Clozapine- and olanzapine-induced hyperglycemia occurred at free plasma concentrations that were within, or one order of magnitude above, the range of therapeutic plasma levels. Pretreatment with either the ganglionic blocker hexamethonium, or the {alpha}2 adrenergic receptor antagonist yohimbine, blocked the clozapine- and chlorpromazine-induced increase in glucose levels. Taken together, these results suggest that typical and atypical antipsychotics with known metabolic liability produce acute hyperglycemia in mice and that this effect is likely driven by activation of the sympathetic autonomic nervous system via a central mechanism.

Keywords: antipsychotic / hyperglycemia / insulin / mouse


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.