Relationships between tricyclic antidepressant concentrations, 1-3H-noradrenaline uptake and chronotropic effect in isolated rat atria

Antonio S. Mundo, Aurora Bonaccorsi, Silvio R. Bareggi, Rosetta Franco, Paolo L. Morselli, Emma Riva, Silvio Garattini

Research output: Contribution to journalArticlepeer-review

Abstract

The uptake of imipramine-14C, desipramine-14C, amitriptyline-14C and chlorimipramine-14C was studied in rat isolated atria incubated in a medium containing concentrations of the drugs ranging from 10-8 to 10-5 M: the tissue levels were linearly related to the concentration in the incubation medium, the four lines sharing almost the same equation: accumulation appeared to be a passive unsaturable process for each drug. Desmethyldoxepin, desmethyl-chlorimipramine, nortriptyline were 4-5 times less potent than desipramine in inhibiting l-3H-noradrenaline uptake, while the tertiary amines (imipramine, amitriptyline, chlorimipramine and doxepin) were far less potent. Apart from desipramine, which showed some sympathomimetic activity, the main effect of the drugs was a slowing of the spontaneous atrial rate which was more evident for the dimethyl than for the monomethyl compounds. All drugs potentiated l-noradrenaline chronotropic response to varying degrees, but the potentiation of noradrenaline response was not always correlated with the inhibition of its uptake. Thus, inhibition of uptake is not a valid parameter for prediction of noradrenaline potentiation and vice versa. Drug tissue concentrations correlated with l-3H-noradrenaline uptake inhibition but not with potentiation of l-noradrenaline chronotropic response.

Original languageEnglish
Pages (from-to)368-375
Number of pages8
JournalEuropean Journal of Pharmacology
Volume28
Issue number2
DOIs
Publication statusPublished - 1974

Keywords

  • 1-H-NA uptake
  • 1-NA chronotropic response
  • Isolated atria
  • Tissue levels
  • Tricyclic antidepressants

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Fingerprint

Dive into the research topics of 'Relationships between tricyclic antidepressant concentrations, 1-3H-noradrenaline uptake and chronotropic effect in isolated rat atria'. Together they form a unique fingerprint.

Cite this