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 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.
D000639:Amitriptyline / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001923:Brain Chemistry / Q000187:drug effects*; D002746:Chlorpromazine / Q000494:pharmacology; D007031:Hypothalamus / Q000648:ultrastructure; D007099:Imipramine / Q000494:pharmacology; D066298:In Vitro Techniques; D007488:Iprindole / Q000494:pharmacology; D008745:Methylation; D009474:Neurons / Q000378:metabolism* / Q000502:physiology; D009661:Nortriptyline / Q000494:pharmacology; D011395:Promazine / Q000494:pharmacology; D051381:Rats; D012701:Serotonin / Q000378:metabolism / Q000502:physiology*; D012702:Serotonin Antagonists; D013329:Structure-Activity Relationship; D013574:Synaptosomes / Q000378:metabolism*
D000928:Antidepressive Agents; D012702:Serotonin Antagonists; D000639:Amitriptyline; D012701:Serotonin; D007488:Iprindole; D009661:Nortriptyline; D011395:Promazine; D007099:Imipramine; D002746:Chlorpromazine