Antagonism by olanzapine of dopamine D1, serotonin2, muscarinic, histamine H1 and alpha 1-adrenergic receptors in vitro.
Article Details
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Bymaster FP, Nelson DL, DeLapp NW, Falcone JF, Eckols K, Truex LL, Foreman MM, Lucaites VL, Calligaro DO
Antagonism by olanzapine of dopamine D1, serotonin2, muscarinic, histamine H1 and alpha 1-adrenergic receptors in vitro.
Schizophr Res. 1999 May 4;37(1):107-22.
- PubMed ID
- 10227113 [ View in PubMed]
- Abstract
The atypical antipsychotic olanzapine has relatively high affinity for a number of neuronal receptors in radioreceptor binding assays. The ability of olanzapine to activate or antagonize a number of neuronal receptors was investigated in vitro, in cell lines transfected selectively with receptor subtypes and in receptor-selective isolated tissue studies. Olanzapine had no agonist activity at any of the receptors examined. However, olanzapine was a potent antagonist of 5-HT-stimulated increases in IP3 in cell lines transfected with 5-HT2A or 5-HT2B receptors with IC50 values of 30-40 nM. Olanzapine weakly blocked 5-HT-induced formation of IP3 in cell lines transfected with 5-HT2c receptors, but in this cell line potently inhibited 5-HT-stimulated [35S]GTP gamma S binding with a Ki value of 15 nM. Olanzapine blocked dopamine-stimulated adenylyl cyclase in rat retina with modest potency (Ki = 69 nM), consistent with its relatively low affinity for dopamine D1 receptors. Olanzapine blocked agonist-induced activities at the muscarinic receptor subtypes M1, M2, M3, and M5 with Ki values of 70, 622, 126, and 82 nM, respectively. In studies using cell lines transfected with muscarinic M4 receptors, olanzapine and the atypical antipsychotic clozapine did not have agonist activities as determined with cAMP inhibition and stimulation assays, arachidonic acid release and [35S]GTP gamma S binding assays. However, olanzapine antagonized agonist-induced effects in muscarinic M4 cells with a Ki value of 350 nM. In isolated tissue studies, olanzapine potently blocked agonist-induced effects at alpha 1-adrenergic and histamine H1 receptors (KB = 9 and 19 nM, respectively). Thus, olanzapine was an antagonist at all receptors investigated and was a particularly potent antagonist at 5-HT2A, 5-HT2B, 5-HT2C, alpha 1-adrenergic and histamine H1 receptors. Olanzapine was a weaker antagonist at muscarinic and dopamine D1 receptors.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Olanzapine 5-hydroxytryptamine receptor 2A Protein Humans YesAntagonistDetails Olanzapine 5-hydroxytryptamine receptor 2C Protein Humans UnknownAntagonistDetails Olanzapine Alpha-1A adrenergic receptor Protein Humans UnknownAntagonistDetails Olanzapine Alpha-1B adrenergic receptor Protein Humans UnknownAntagonistDetails Olanzapine Dopamine D1 receptor Protein Humans UnknownAntagonistDetails Olanzapine Dopamine D5 receptor Protein Humans UnknownAntagonistDetails Olanzapine Histamine H1 receptor Protein Humans UnknownAntagonistDetails Olanzapine Muscarinic acetylcholine receptor M1 Protein Humans UnknownAntagonistDetails Olanzapine Muscarinic acetylcholine receptor M2 Protein Humans UnknownAntagonistDetails Olanzapine Muscarinic acetylcholine receptor M3 Protein Humans UnknownAntagonistDetails Olanzapine Muscarinic acetylcholine receptor M4 Protein Humans UnknownAntagonistDetails - Binding Properties
Drug Target Property Measurement pH Temperature (°C) Olanzapine 5-hydroxytryptamine receptor 2C Ki (nM) 29 N/A N/A Details Olanzapine Muscarinic acetylcholine receptor M1 Ki (nM) 2.5 N/A N/A Details Olanzapine Muscarinic acetylcholine receptor M3 Ki (nM) 13 N/A N/A Details Olanzapine Muscarinic acetylcholine receptor M4 Ki (nM) 10 N/A N/A Details