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Inverse agonist properties of atypical antipsychotic drugs

Akam, E. and Strange, P. G. (2004) Inverse agonist properties of atypical antipsychotic drugs. Biochemical Pharmacology, 67 (11). pp. 2039-2045. ISSN 0006-2952

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To link to this item DOI: 10.1016/j.bcp.2004.02.017


Mechanisms of action of several atypical antipsychotic drugs have been examined at the D-2 dopamine receptor expressed in CHO cells. The drugs tested were found to exhibit inverse agonist activity at the D-2 dopamine receptor based on their effects to potentiate forskolin-stimulated cyclic AMP (cAMP) accumulation. Each of the antipsychotic drugs tested (clozapine, olanzapine, quetiapine and risperidone) increased cAMP accumulation to the same extent. The increase in cAMP was also similar to that seen with typical antipsychotic drugs. Inverse agonism at the D-2 dopamine receptor seems, therefore, to be a property common to all classes of antipsychotic drugs. The effect of sodium ions on the binding of the drugs to the receptor was also assessed. Each of the atypical antipsychotic drugs tested here bound with higher affinity in the absence of sodium ions. Previous studies have shown that some antipsychotic drugs are insensitive to sodium ions and some bind with higher affinity in the presence of sodium ions. Given that all of these antipsychotic drugs are inverse agonists, it may be concluded that this sodium ion sensitivity is unrelated to mechanisms of inverse agonism. (C) 2004 Elsevier Inc. All rights reserved.

Item Type:Article
Divisions:Life Sciences > School of Biological Sciences
ID Code:10410
Uncontrolled Keywords:D-2, dopamine receptor, inverse agonism, atypical antipsychotic drugs, cAMP, sodium ion sensitivity, mechanism, PROTEIN-COUPLED RECEPTORS, DOPAMINE D2 RECEPTORS, CONSTITUTIVE, ACTIVITY, D-3 RECEPTOR, MECHANISMS, DEFINITION, BINDING, LIGAND

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