In vivo occupancy of dopamine D2 receptors by antipsychotic drugs and novel compounds in the mouse striatum and olfactory tubercles
| Autor: | Nathalie Consul-Denjean, Marie-Bernadette Assié, Adrian Newman-Tancredi, Hélène Dominguez |
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| Rok vydání: | 2006 |
| Předmět: |
Male
medicine.medical_specialty Apomorphine Bifeprunox Pharmacology Binding Competitive chemistry.chemical_compound Mice Eticlopride Dopamine Internal medicine Dopamine receptor D2 medicine Animals Receptor Clozapine Raclopride Catalepsy Behavior Animal Dose-Response Relationship Drug Receptors Dopamine D2 Nemonapride General Medicine Olfactory Bulb Serotonin Receptor Agonists Neostriatum Endocrinology chemistry Benzamides Dopamine Agonists Dopamine Antagonists medicine.drug Antipsychotic Agents |
| Zdroj: | Naunyn-Schmiedeberg's archives of pharmacology. 373(6) |
| ISSN: | 0028-1298 |
| Popis: | Interaction with dopamine D2-like receptors plays a major role in the therapeutic effects of antipsychotic drugs. We examined in vivo dopamine D2 receptor occupancy of various established and potential antipsychotics in mouse striatum and olfactory tubercles 1 h after administration of the compound, using [3H]nemonapride as a ligand. All the compounds reduced in vivo binding of [3H]nemonapride in the striatum. When administered systemically, conventional antipsychotics, D2 antagonists, nemonapride (ID50: 0.034 mg/kg), eticlopride (0.047), haloperidol (0.11) and raclopride (0.11) potently inhibited [3H]nemonapride binding. The 'atypical' antipsychotics, risperidone (0.18), ziprasidone (0.38), aripiprazole (1.6), olanzapine (0.99), and clozapine (11.1) were less potent for occupying D2-like receptors. New compounds, displaying marked agonism at 5-HT1A receptors in addition to D2 receptor affinity, exhibited varying D2 receptor occupancy: bifeprunox (0.25), SLV313 (0.78), SSR181507 (1.6) and sarizotan (6.7). ID50 values for inhibition of [3H]nemonapride binding in the striatum correlated with those in the olfactory tubercles (r=0.95, P |
| Databáze: | OpenAIRE |
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