JPET Assistant Professor of Medicine (Clinician-Educator)

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
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 Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Saller, C. F.
Right arrow Articles by Salama, A. I.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Saller, C. F.
Right arrow Articles by Salama, A. I.

5-HT2 receptor blockade by ICI 169,369 and other 5-HT2 antagonists modulates the effects of D-2 dopamine receptor blockade

CF Saller, MJ Czupryna and AI Salama

Biomedical Research, ICI Pharma, a Business Unit of ICI Americas, Inc., Wilmington, Delaware.

The effects of D-2 dopamine (DA) receptor blockade were modulated by ICI 169,369, a selective 5-hydroxytryptamine (5-HT)2 receptor antagonist, and by other 5-HT2 antagonists. Specifically, it appears that blockade of 5-HT2 receptors can attenuate the effects of D-2 receptor blockade on rat striatal dopaminergic transmission. Thus, the blockade of D-2 receptors by haloperidol results in a compensatory increase in rat striatal DA metabolism, which is enhanced by ICI 169,369. By itself, ICI 169,369 did not significantly alter DA metabolism. Conversely, several compounds which possess appreciable activity at 5-HT2 sites in ex vivo binding assays, but possess little activity at D-2 sites (i.e., pirenperone, setoperone, fluperlapine and clozapine), all produced large increases in striatal DA metabolism. Therefore, these data suggest that the 5-HT2 component of these compounds, by enhancing DA metabolism, may act to attenuate the blockade of striatal D-2 receptors by these compounds. Consistent with this hypothesis, the chronic blockade of D-2 receptors by haloperidol increases the number of striatal D-2 DA receptors, and these increases are attenuated by the coadministration of ICI 169,369. Likewise, pirenperone and clozapine, at doses which acutely produced elevations in DA metabolism which were similar to those produced by haloperidol, failed to increase the number of D-2 receptors in striatum. Interestingly, 5-HT2 receptor blockade did not appear to potently modulate the effects of D-2 receptor blockade in the olfactory tubercle, a brain region which is innervated by mesolimbic DA- containing neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

Volume 253, Issue 3, pp. 1162-1170, 06/01/1990
Copyright © 1990 by American Society for Pharmacology and Experimental Therapeutics




This article has been cited by other articles:


Home page
 J. Pharmacol. Exp. Ther.Home page
L. R. Gardell, K. E. Vanover, L. Pounds, R. W. Johnson, R. Barido, G. T. Anderson, I. Veinbergs, A. Dyssegaard, P. Brunmark, A. Tabatabaei, et al.
ACP-103, a 5-Hydroxytryptamine 2A Receptor Inverse Agonist, Improves the Antipsychotic Efficacy and Side-Effect Profile of Haloperidol and Risperidone in Experimental Models
J. Pharmacol. Exp. Ther., August 1, 2007; 322(2): 862 - 870.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 1990 by the American Society for Pharmacology and Experimental Therapeutics.