Aripiprazole's low intrinsic activities at human dopamine D2L and D2S receptors render it a unique antipsychotic
| Autor: | Arlene Stark, Takashi Miwa, Toyoki Mori, Yoshihiro Tadori, Kevin D. Burris, Katsura Tottori, Tetsuro Kikuchi |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
medicine.medical_specialty
DNA Complementary medicine.drug_class Dopamine Bifeprunox Aripiprazole Atypical antipsychotic CHO Cells Pharmacology Quinolones Transfection Tritium Terguride Partial agonist Binding Competitive Piperazines Radioligand Assay Cricetulus Piperidines Internal medicine Dopamine receptor D2 Cricetinae medicine Cyclic AMP Animals Humans Receptor Lisuride Chemistry Receptors Dopamine D2 Cell Membrane Colforsin Risperidone Endocrinology Raclopride Dopamine Agonists Dopamine Antagonists Haloperidol medicine.drug Antipsychotic Agents |
| Zdroj: | European journal of pharmacology. 515(1-3) |
| ISSN: | 0014-2999 |
| Popis: | Aripiprazole is the first clinically approved atypical antipsychotic agent having dopamine D2 receptor partial agonist activities. To evaluate aripiprazole's agonist and antagonist properties, we established a Chinese hamster ovary cell line expressing high and low densities of the long and short isoforms of human dopamine D2 receptors, then compared its properties with 7-{3-[4-(2,3-dimethylphenyl)piperazinyl]propoxy}-2(1H)-quinolinone (OPC-4392), S(-)-3-(3-hydroxyphenyl)-N-n-propylpiperidine ((-)-3-PPP), and terguride (other partial agonists) using forskolin-stimulated cAMP accumulation as an index. In cells expressing high receptor densities, all partial agonists predominantly behaved as agonists. However, in cells expressing low receptor densities, the partial agonists showed significantly lower maximal effects than dopamine. Aripiprazole showed the lowest intrinsic activities. In addition, all compounds blocked the action of dopamine with a maximum effect equal to that of each compound alone. Aripiprazole's low intrinsic activities may account for the clinical finding that, unlike the other partial agonists, it is substantially active against both positive and negative symptoms of schizophrenia. |
| Databáze: | OpenAIRE |
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