Structure-activity relations for the inhibition of 5-hydroxytryptamine uptake by tricyclic antidepressants into synaptosomes from serotoninergic neurones in rat brain homogenates

1 The inhibitory effects of various analogues of imipramine on [(3)H]-5-hydroxytryptamine (5-HT) uptake into homogenates of rat hypothalamus were examined.2 For structures with a three carbon side chain the tertiary amine derivative was more potent than the compound with a secondary amine function.3...

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Bibliographic Details
Published in:British journal of pharmacology 1974-07, Vol.51 (3), p.399-403
Main Authors: Horn, A S, Trace, R C
Format: Article
Language:English
Subjects:
Amitriptyline - pharmacology
Animals
Antidepressive Agents - pharmacology
Brain Chemistry - drug effects
Chlorpromazine - pharmacology
Hypothalamus - ultrastructure
Imipramine - pharmacology
In Vitro Techniques
Iprindole - pharmacology
Methylation
Neurons - metabolism
Neurons - physiology
Nortriptyline - pharmacology
Pharmacokinetics
Promazine - pharmacology
Rats
Serotonin - metabolism
Serotonin - physiology
Serotonin Antagonists
Structure-Activity Relationship
Synaptosomes - metabolism
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Summary:1 The inhibitory effects of various analogues of imipramine on [(3)H]-5-hydroxytryptamine (5-HT) uptake into homogenates of rat hypothalamus were examined.2 For structures with a three carbon side chain the tertiary amine derivative was more potent than the compound with a secondary amine function.3 Potency was reduced by increasing or decreasing the length of the three carbon side chain by one carbon atom.4 Substitution of a methyl group in the alpha or beta position in the side chain reduced potency.5 Replacement of the dimethylene bridge in imipramine by a sulphur atom or substitution of a C=C double bond for the exocyclic N-C bond of imipramine both led to a fall in potency.6 3-Chlorimipramine was the most potent inhibitor of [(3)H]-5-hydroxytryptamine uptake of the compounds tested.
ISSN:0007-1188