Article date: April 1978
By: KIN SHEIN, S.E. SMITH in Volume 62, Issue 4, pages 567-571
The anticholinoceptor action of 15 tricyclic antidepressants and derivatives has been studied on the guinea‐pig ileum. At the muscarinic receptors the compounds were found to exert antagonism which was reversible and apparently competitive up to dose‐ratios of around 100 but non‐competitive above this level.
Log affinity constants were derived from log dose‐response curves at dose‐ratios <100, where parallel curves were obtained. Amitriptyline, the most potent compound, had 214 × the potency of the weakest, hydroxyimipramine, but was itself 20 × weaker than atropine.
Structure‐activity studies showed that dibenzocycloheptane derivatives were more potent than dibenzazepines and that S or O substitution for C‐11 or other major changes in the central ring of the tricyclic nucleus greatly reduced activity. Side‐chain N‐methylation increased potency markedly. This and other findings indicate that both tricyclic nucleus and side‐chain receptor attachments are largely non‐polar in type.
The anticholinoceptor action of 15 tricyclic antidepressants and derivatives has been studied on the guinea‐pig ileum. At the muscarinic receptors the compounds were found to exert antagonism which was reversible and apparently competitive up to dose‐ratios of around 100 but non‐competitive above this level.
Log affinity constants were derived from log dose‐response curves at dose‐ratios <100, where parallel curves were obtained. Amitriptyline, the most potent compound, had 214 × the potency of the weakest, hydroxyimipramine, but was itself 20 × weaker than atropine.
Structure‐activity studies showed that dibenzocycloheptane derivatives were more potent than dibenzazepines and that S or O substitution for C‐11 or other major changes in the central ring of the tricyclic nucleus greatly reduced activity. Side‐chain N‐methylation increased potency markedly. This and other findings indicate that both tricyclic nucleus and side‐chain receptor attachments are largely non‐polar in type.
DOI: 10.1111/j.1476-5381.1978.tb07763.x
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