Potent antagonism of 5-HT3 and 5-HT6 receptors by olanzapine
| Autor: | Delbert Bauzon, Neil W. DeLapp, Frank P. Bymaster, Julie F. Falcone, Marlene L. Cohen, Kathryn W. Schenck, John S. Kennedy |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Olanzapine
Agonist Dibenzothiazepines Serotonin medicine.medical_specialty Indoles medicine.drug_class Guinea Pigs Tropisetron GTPgammaS Atypical antipsychotic In Vitro Techniques Pharmacology Sulfur Radioisotopes Tritium Binding Competitive Benzodiazepines Quetiapine Fumarate chemistry.chemical_compound Ileum Internal medicine medicine Animals Humans Receptor Clozapine 5-HT receptor Lysergic Acid Dose-Response Relationship Drug Chemistry Pirenzepine Risperidone Receptor antagonist Ondansetron Serotonin Receptor Agonists Endocrinology Guanosine 5'-O-(3-Thiotriphosphate) Receptors Serotonin Haloperidol Serotonin Antagonists Receptors Serotonin 5-HT3 Selective Serotonin Reuptake Inhibitors HeLa Cells Muscle Contraction medicine.drug |
| Zdroj: | European Journal of Pharmacology. 430:341-349 |
| ISSN: | 0014-2999 |
| Popis: | The interaction of the psychotropic agent olanzapine with serotonin 5-HT(3) and 5-HT(6) receptors was investigated. Olanzapine did not contract the isolated guinea pig ileum, but blocked contractions induced by the 5-HT(3) receptor agonist 2-methyl serotonin (2-CH(3) 5-HT) with a pK(B) value of 6.38+/-0.03, close to the affinity of the 5-HT(3) receptor antagonist ondansetron. The atypical antipsychotic risperidone (1 microM) did not significantly inhibit 2-CH(3) 5-HT-induced contractions. Olanzapine had high affinity (pK(i)=8.30+/-0.06) for human 5-HT(6) receptors in radioligand binding studies. Olanzapine did not stimulate [35S]guanosine-5'-O-(3-thio)triphosphate ([35S]GTPgammaS) binding to the G protein G(s) in cells containing human 5-HT(6) receptors, but inhibited 5-HT-stimulated [35S]GTPgammaS binding (pK(B)=7.38+/-0.16). Among other antipsychotics investigated, clozapine antagonized 5-HT(6) receptors with a pK(B)=7.42+/-0.15, ziprasidone was three-fold less potent, and risperidone, quetiapine and haloperidol were weak antagonists. Thus, olanzapine was not an agonist, but was a potent antagonist at 5-HT(6) receptors and had marked antagonism at 5-HT(3) receptors. |
| Databáze: | OpenAIRE |
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