Abstract
The synthesis and resolution of 1,2,3,4,10,14b-hexahydro-6-methoxy-2-methyldibenzo[c,f]pyrazino[1,2-a]azepin (6-methoxymianserin, 6) are described. Furthermore, the in vitro and in vivo effects of 6 and its enantiomers are presented. 6 displayed high affinity for the 5-HT2A/2C receptors, only moderate affinity for the adrenoceptors, and no affinity for the NA reuptake site. Surprisingly, 6 also showed moderate to high affinity for the dopamine D2 receptor, an effect that resides in the (R)-(-)-enantiomer.
MeSH terms
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3,4-Dihydroxyphenylacetic Acid / metabolism
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Animals
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Antidepressive Agents / chemical synthesis*
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Antidepressive Agents / chemistry
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Antidepressive Agents / pharmacology*
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Binding Sites
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Hippocampus / drug effects
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Hippocampus / metabolism
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Hydroxyindoleacetic Acid / metabolism
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In Vitro Techniques
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Male
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Mianserin / analogs & derivatives*
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Mianserin / chemical synthesis*
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Mianserin / chemistry
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Mianserin / pharmacology*
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Microdialysis
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Mirtazapine
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Norepinephrine / metabolism
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Radioligand Assay
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Rats
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Rats, Wistar
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Receptors, Adrenergic / metabolism
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Receptors, Dopamine / metabolism
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Receptors, Histamine / metabolism
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Receptors, Serotonin / metabolism
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Serotonin / metabolism
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Stereoisomerism
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Structure-Activity Relationship
Substances
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6-methoxymianserin
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Antidepressive Agents
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Receptors, Adrenergic
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Receptors, Dopamine
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Receptors, Histamine
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Receptors, Serotonin
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3,4-Dihydroxyphenylacetic Acid
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Mianserin
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Serotonin
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Hydroxyindoleacetic Acid
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Mirtazapine
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Norepinephrine