Arrhythmias and inhibition of noradrenaline uptake caused by tricyclic antidepressants and chlorpromazine on the isolated perfused rabbit heart

  title={Arrhythmias and inhibition of noradrenaline uptake caused by tricyclic antidepressants and chlorpromazine on the isolated perfused rabbit heart},
  author={N. Barth and Markus Manns and Erich Muscholl},
  journal={Naunyn-Schmiedeberg's Archives of Pharmacology},
Summary1.Isolated rabbit hearts were perfused with a modified Tyrode solution containing noradrenaline in concentrations increasing stepwise from 5.9 nM to 5.9 μM at 5 min intervals. This dose regime was applied twice before and once 20 min after starting perfusion with one of 9 tricyclic drugs. Ventricular rate and right atrial and ventricular tensions were recorded using the transverse method.2.Infusions of noradrenaline evoked ventricular arrhythmias in hearts perfused with amitriptyline 4.8… 

The effect of tricyclic antidepressant drugs on the heart

The guinea-pig provides a good model for studying the arrhythmogenic actions of tricyclic antidepressants and doxepin was the most potent cardio-depressant in the spontaneously beating atrial preparation.

Effects of 5-hydroxytryptamine and related compounds on the sympathetic nerves of the rabbit heart

Findings confirm that the positive chronotropic effects of indolethylamines on the rabbit heart are due to noradrenaline release.


  • I. Hughes
  • Biology, Chemistry
    British journal of pharmacology
  • 1978
It is concluded that amitriptyline may raise synaptic levels of noradrenaline by blocking presynaptic α‐adrenoceptors controlling norADrenaline release and by blocking its uptake into sympathetic neurones.


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Inhibition of noradrenaline release from sympathetic nerves by pentobarbital

Pentobarbital concentrations of 10–100 μM selectively inhibited the noradrenaline release evoked by activation of the nicotinic receptors on the terminals sympathetic nerves of the rabbit heart.

Doxepin Up-to-Date: A Review of its Pharmacological Properties and Therapeutic Efficacy with Particular Reference to Depression

The more marked sedative properties of doxepin make it more useful than imipramine in depressed patients with sleep disturbances and in depression associated with anxiety, and it has an intrinsic cardiotoxicity on overdosage similar to other tricyclic antidepressants.

Review of the cardiovascular toxicity of amitriptyline treatment for canine neuropathic pain

The aim of this review is to highlight the importance of routine cardiovascular monitoring and to provide a list of parameters that are associated with amitriptyline cardiovascular toxicity.

The role of pharmacological profiling in safety assessment.

  • P. Williams
  • Biology, Medicine
    Regulatory toxicology and pharmacology : RTP
  • 1990



The effects of the tricyclic antidepressants desipramine, doxepin and iprindole on the isolated perfused rabbit heart

It is concluded that the combination of noradrenaline release by nerve stimulation and atrioventricular blockade by tricyclic antidepressants is responsible for the arrhythmia-producing effect observed in the present study.

Interactions between Sympathomimetic Amines and Antidepressant Agents in Man

Noradrenaline and adrenaline in amounts contained in local anaesthetics used in dentistry are not likely to be significantly potentiated in otherwise healthy patients receiving monoamine oxidase inhibitors, and Hazardous potentiation of their cardiovascular effects might occur in patients receiving tricyclic antidepressants.

Uptake of3H-noradrenaline by adrenergic nerves of rat iris incubated in plasma from patients treated with various psychotropic drugs

SummaryRat iris, which is richly innervated by adrenergic nerves, was incubated with3H-noradrenaline (3H-NA) in plasma from patients receiving clinical treatment with chlorpromazine, thioridazine,

Effect of drugs on the uptake and metabolism of H3-norepinephrine.

The catechol-O-methyl transferase inhibitor, pyrogallol, elevated the concentration of H 3 - norepinephrine in heart, spleen, liver and muscle but not the adrenal gland and plasma, and lowered the concentration in these tissues except the heart and spleen.

A useful muscarinic parameter and the differential recording of atrial and ventricular tension in the perfused rabbit heart

Besides providing an additional pharmacological parameter, measurement of right atrial tension affords a useful method of detecting muscarinic activity in those drugs (e.g. ganglion stimulants) which have mixed parasympathetic and sympathetic cardiac actions.


In 45 of thc patients the systolic and diastolic pressures decreased on an average by 20-30 mm Hg, but there was no definite correlation with alterations in the ECG.

Molecular features affecting the potency of tricyclic antidepressants and structurally related compounds as inhibitors of the uptake of tritiated norepinephrine by rabbit aortic strips.

Molecular models reveal that the kinetics for the uptake of norepinephrine by aortic strips in the presence and absence of the inhibitors indicates that both substances compete for the same active site in the adrenergic nerve membrane.

Inhibition of 3H‐metaraminol uptake by antidepressive and related agents

Investigation to a number of other antidepressive and related agents found that reserpine, a drug acting on the granular storage mechanism, did not inhibit the initial uptake of 3Hmetaraminol but greatly increased its rate of disappearance.