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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Seeman, Philip |
| Description | Country affiliation: Canada Author Affiliation: Seeman P ( Department of Pharmacology, Medical Science Building, University of Toronto, Toronto, Ontario, Canada. philip.seeman@utoronto.ca) |
| Abstract | Because long-term antipsychotics elicit behavioral dopamine supersensitivity, the present study examined whether 7-9 days administration of partial dopamine D2 agonists with antipsychotic activity, bifeprunox and aripiprazole, could induce biochemical changes that suggest dopamine supersensitivity. In rats, behavioral dopamine supersensitivity is associated with increased dopamine D2(High) receptors in homogenized striata. In control rat striata, bifeprunox and aripiprazole had similar K(i) values at D2 receptors. In human cloned D2Long receptors, however, aripiprazole had a K(i) of 9.6 nM and recognized 41% of the D2 receptors to be in the D2(High) state, while the values for bifeprunox were 1.3 nM and 69%, indicating that bifeprunox had higher potency and efficacy at D2. Nine days of subcutaneously injected bifeprunox (0.25 mg/kg/day) and 7 days of aripiprazole (1.5 mg/kg) increased D2(High) receptors by 102-129% and 108-188%, respectively, although the total population of D2 receptors revealed no significant changes. The increase in D2(high) receptors induced by dopamine D2 partial agonists appear to be of smaller magnitude than those seen previously with D2 antagonist antipsychotics. Future research needs to test directly whether long-term treatment with dopamine partial agonists leads to any behavioral dopamine supersensitivity. |
| File Format | HTM / HTML |
| ISSN | 08874476 |
| Issue Number | 12 |
| Volume Number | 62 |
| e-ISSN | 10982396 |
| Journal | Synapse |
| Language | English |
| Publisher | Wiley |
| Publisher Date | 2008-12-01 |
| Publisher Place | United States |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Discipline Neurology Benzoxazoles Pharmacology Piperazines Quinolones Receptors, Dopamine D2 Biosynthesis Animals Aripiprazole Metabolism Cho Cells Cricetinae Cricetulus Dopamine Agonists Dopamine Antagonists Dopamine D2 Receptor Antagonists Dose-response Relationship, Drug Humans Protein Binding Drug Effects Physiology Rats Rats, Sprague-dawley Agonists Comparative Study Journal Article Research Support, Non-u.s. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cellular and Molecular Neuroscience |
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