Abstract
In previous articles we have described the discovery of a new series of tricyclic isoxazolines combining central serotonin (5-HT) reuptake inhibition with alpha(2)-adrenoceptor antagonistic activity. We report now on the synthesis, the in vitro binding potency and the primary in vivo activity of six enantiomers within this series, one of which was selected for further pharmacological evaluation and assigned as R226161. Some additional in vivo studies in rats are described with this compound, which proved to be centrally and orally active as a combined 5-HT reuptake inhibitor and alpha(2)-adrenoceptor antagonist.
MeSH terms
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Adrenergic alpha-2 Receptor Antagonists*
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Animals
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Antidepressive Agents, Tricyclic / chemical synthesis
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Antidepressive Agents, Tricyclic / chemistry*
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Antidepressive Agents, Tricyclic / pharmacology*
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Humans
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Isoxazoles / chemical synthesis
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Isoxazoles / chemistry*
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Isoxazoles / pharmacology*
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Male
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Oxazoles / chemical synthesis
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Oxazoles / chemistry*
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Oxazoles / pharmacology*
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Pyrazines / chemical synthesis
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Pyrazines / chemistry*
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Pyrazines / pharmacology*
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Rats
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Rats, Wistar
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Selective Serotonin Reuptake Inhibitors / chemical synthesis
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Selective Serotonin Reuptake Inhibitors / chemistry*
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Selective Serotonin Reuptake Inhibitors / pharmacology*
Substances
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Adrenergic alpha-2 Receptor Antagonists
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Antidepressive Agents, Tricyclic
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Isoxazoles
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Oxazoles
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Pyrazines
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R226161
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Serotonin Uptake Inhibitors