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Dopamine D2 High receptors moderately elevated by bifeprunox and aripiprazole
Author(s) -
Seeman Philip
Publication year - 2008
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.20557
Subject(s) - aripiprazole , dopamine receptor d2 , dopamine , partial agonist , chemistry , dopamine receptor , medicine , receptor , endocrinology , antipsychotic , dopamine receptor d3 , pharmacology , population , antagonist , psychology , schizophrenia (object oriented programming) , psychiatry , environmental health
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. Synapse 62:902–908, 2008. © 2008 Wiley‐Liss, Inc.