Responses to tyramine and norepinephrine after imipramine and trazodone

Larochelle, Pierre; Hamet, Pavel; Enjalbert, M

doi:10.1002/cpt197926124

Cited by 25 publications

(10 citation statements)

References 6 publications

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“…In every respect, except one, trazodone lived up to the benign cardiovascular profile predicted by the animal and human studies of Gomoll [21,22], Gomoll and Byrne [23] and La Rochelle et al [24] reviewed by llimmelhoch [25] in 1981. The problem still in question is the observation of Janowskyex al.…”

Section: Cardiovascular Effects O F Trazodonementioning

confidence: 99%

The Role of Trazodone in the Treatment of Depressed Cardiac Patients

Himmelhoch¹,

Schechtman²,

Auchenbach³

1984

Psychopathology

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The novel antidepressant trazodone is hypothesized to be less cardiotoxic than the tri-tetracyclic antidepressants. Recently, however, 2 patients with preexisting ventricular irritability showed an increased number of ventricular premature beats and of repetitive forms after starting on trazodone. Data are presented here from four studies on the cardiovascular safety of trazodone. Conclusions are: (1) Trazodone has little effect on cardiac conduction. (2) Trazodone does not worsen supraventricular arrhythmias. (3) Trazodone produces less postural hypotension than most other antidepressants and it tends to lower heart rate. (4) Lower doses of trazodone (100–300 mg) are better tolerated and more effective in major depressives simultaneously debilitated by significant cardiovascular disease. (5) It is possible that the so-called ‘trazodone aggravation’ of ventricular irritability is a statistical artifact – although further research is needed to verify this conclusion, and in the meantime the drug should be used with caution in such patients.

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Section: Cardiovascular Effects O F Trazodonementioning

confidence: 99%

The Role of Trazodone in the Treatment of Depressed Cardiac Patients

Himmelhoch¹,

Schechtman²,

Auchenbach³

1984

Psychopathology

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“…In a study in human subjects (Larochelle, Hamet & Enjalbert, 1979), a single dose (25 mg) of imipramine did not affect pressor responses to tyramine, although daily administration of this dose for several days reduced responses to tyramine and potentiated those to noradrenaline. In the same study it was shown that trazodone did not affect pressor responses to the sympathomimetic amines.…”

Section: Discussionmentioning

confidence: 91%

Effects of LM 5008, a selective inhibitor of 5‐hydroxytryptamine uptake, on blood pressure and responses to sympathomimetic amines

Ashkenazi

Finberg

Youdim

1983

British J Pharmacology

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1 LM 5008 (4-[2-(3-indolyl)ethyl]piperidine) (10,20 and 50 mgkg-) had no significant effect on pressor responses to noradrenaline or tyramine in rats anaesthetized with urethane. Desmethylimipramine (1 mg kg-1) blocked the response to tyramine but chlorimipramine (5 mg kg-1) had no significant effect on responses to noradrenaline or tyramine. 2 In the rabbit, anaesthetized with chloralose, LM 5008 (5 mg kg-') had no effect on pressor responses to noradrenaline, tyramine or angiotensin II, while desmethylimipramine (0.25 mg kg-1) inhibited responses to tyramine and potentiated those to noradrenaline.3 LM 5008 (10mg kg-') had no effect on resting blood pressure of conscious normotensive or DOCA-saline hypertensive rats. 4 Tranylcypromine (5 mg kg-) produced a fall in blood pressure in conscious normotensive and in DOCA hypertensive rats.5 Treatment with a combination of LM5008 (10mgkg-t) and tranylcypromine (5mgkg-1) resulted in the appearance of a behavioural hyperactivity syndrome, but blood pressure was not different from that of animals treated with tranylcypromine alone. 6 These results further demonstrate the selectivity of LM 5008 for 5-hydroxytryptamine as opposed to catecholamine uptake.

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“…It is thought to act by the selective inhibition of serotonin reup take [19,22]; norepinephrine inhibition oc curs only at exceedingly high doses [19]. Its antidepressant activity was first reported in 1967 [23], However, in classical laboratory tests trazodone does not produce the results typical ofantidepressant compounds (table V).…”

Section: Newer Antidepressantsmentioning

confidence: 99%

“…It does not inhibit dopamine or monoamine oxidase, does not potentiate L-dopa or yohim bine toxicity, does not antagonize reserpine, and has no anticonvulsant action [22], In vitro and in animals, the behavior of trazodone pointed to an absence of anticho linergic activity [22], In anesthetized dogs, comparisons of the cardiovascular effects of trazodone and imipramine showed trazo done to be far less cardiotoxic than the tricy clic reference drug ( fig. 1, 2) [23], This is pos sibly due to its lack of catecholamine-poten tiating activity [19].…”

Section: Newer Antidepressantsmentioning

confidence: 99%

Comparative Side Effect Profiles of Trazodone and Imipramine: Special Reference to the Geriatric Population

Gershon¹

1984

Psychopathology

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Side effects are a concomitant of almost all therapeutic agents and are also present as part of the pharmacological profile of psychotropic agents. However, the laboratory pharmacological characteristics of agents are a more reliable predictor of side effect profiles than they are of their therapeutic activities. Therefore, it would seem possible to be able to predict with much greater accuracy the clinically significant side effects that may be encountered from the preclinical data. This has been established in the case of trazodone and imipramine. The anticholinergic profile of imipramine was clearly determined in the laboratory and in man it produces a range of activity varying from mild peripheral anticholinergic activity to impairment of various functions involving vision, cardiovascular function and gastrointestinal activity. However, in the geriatric population, because of the vast amount of research implicating cholinergic mechanisms in memory functions and particularly in some aspects of cognitive deficit, it may be predicted that the anticholinergic activity of the tricyclics may present an especially troublesome pattern in a geriatric population that requires antidepressant therapy. These comparative effects between the two agents will be discussed and documented from control study data.

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Responses to tyramine and norepinephrine after imipramine and trazodone

Abstract: Responses to tyramine and norepinephrine after imipramine and trazodone

Cited by 25 publications

References 6 publications

The Role of Trazodone in the Treatment of Depressed Cardiac Patients

The Role of Trazodone in the Treatment of Depressed Cardiac Patients

Effects of LM 5008, a selective inhibitor of 5‐hydroxytryptamine uptake, on blood pressure and responses to sympathomimetic amines

Comparative Side Effect Profiles of Trazodone and Imipramine: Special Reference to the Geriatric Population

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