A Possible Mechanism of Central Action of Trazodone in Rats

Yamatsu, Kiyomi; Kaneko, Toyozo; Yamanishi, Yoshihiro; Kitahara, Akio; Ohtake, Shinzaburo

doi:10.1159/000395597

Cited by 10 publications

(6 citation statements)

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“…17 a potent a-adrenolytic drug.!. 15 It inhibits the uptake of norepinephrine only at exceedingly high concentrations, 8,17 but this effect is probably nonspecific and meaningless since trazodone also has local anesthetic properties, It does not potentiate L-dopa and has no significant anticholinergic effect, but does exert an antiserotonin effect l6 , 20 although it has been suggested that it exerts a central serotoninergic effect. 8,11 At least in animals, trazodone seems to be devoid of catecholamine potentiating action, which is thought to be responsible for the cardiotoxicity of tricyclic antidepressants; after intravenous infusion, trazodone does not induce Animals studies have shown that trazodone is the typical electrocardiographic changes of the tricyclic antidepressants.…”

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confidence: 99%

Responses to tyramine and norepinephrine after imipramine and trazodone

Larochelle

Hamet

Enjalbert

1979

Clin Pharma and Therapeutics

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confidence: 99%

Responses to tyramine and norepinephrine after imipramine and trazodone

Larochelle

Hamet

Enjalbert

1979

Clin Pharma and Therapeutics

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“…Different studies report that trazodone usually decreases the amount of rapid eye movement (REM) sleep (Aton et al, 2009; Brogden et al, 1981; Mendelson, 2005; van Bemmel et al, 1992; Yamatsu et al, 1974). However, to our knowledge, only one study investigated the effect of the dose of trazodone on the amount of REM during sleep following administration of this drug (Yamatsu et al, 1974). According to this investigation, the suppression of REM is proportional to the dose of trazodone administered, with low doses having no effect on the amount of REM during sleep (Yamatsu et al, 1974).…”

Section: Discussionmentioning

confidence: 99%

Evaluating the dose-dependent mechanism of action of trazodone by estimation of occupancies for different brain neurotransmitter targets

Settimo

Taylor

2018

J Psychopharmacol

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Trazodone is a drug that was introduced in the clinic almost 40 years ago. It is licensed to treat depression, but it is also commonly used off-label to treat insomnia. A recent study shows that it could be promising in preventing neurodegeneration in mice, and clinical trials to assess its possible beneficial effects on dementia and Alzheimer's disease are expected to start soon in humans. In this study, we describe the dose-dependent pharmacology of trazodone by carrying out pharmacokinetic simulations aiming to predict the brain concentrations of trazodone for different drug-dosing regimens and calculating occupancy for 28 different targets for which published trazodone-binding data are available. Our study indicates that low doses of trazodone (typically 50 mg daily) should suffice to block specific receptors responsible for the hypnotic effect, and to provide the protective effect against neuroinflammation and neurodegeneration that could be beneficial in dementia. Higher doses are required for an antidepressant effect. The occupancy of specific receptors at therapeutic doses also explains peculiar side effects reported by patients treated with trazodone (e.g. dry-mouth, hypotension and priapism).

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“…This approach led to foreseeing the potential usefulness of trazodone and other com pounds in depression despite a pharmacolog ical profile different from that of the tricyclics [Lisciani el al., 1978;Silvestrini, 1980;Silves trini and Lisciani, 1973;Silvestrini et al, 1968], Figure 1 schematically compares the differences between trazodone and imipramine, which is the most typical first-genera tion antidepressant [Boissier et al, 1974;Cioli et al. 1983;Lisciani et al, 1978;Riblet and Taylor, 1981;Lisciani, 1973, 1976;Silvestrini et al, 1968;Yamatsu et al, 1974], Not only is trazodone devoid of the char acteristic peripheral and central adrenergic effects of imipraminc, but it also has opposite actions. Imipramine has an anticholinergic activity which trazodone does not have.…”

Section: Mechanism Of Action Of Antidepressantsmentioning

confidence: 99%

Trazodone, a New Avenue in the Treatment of Depression

Silvestrini¹,

Valeri²

1984

Psychopathology

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Pharmacological and biochemical data on trazodone are reviewed in order to compare this drug to imipramine and other tricyclics both from the point of view of the mechanism of action and preferential clinical indications. Trazodone tends to inhibit biochemical and pharmacological functions depending on the catecholaminergic system, whereas imipramine has a potentiating activity. However, both these drugs decrease the density of β-receptors following repeated administrations. Trazodone and imipramine have similar effects on the serotoninergic system. The two drugs also share an antinociceptive activity. It is stressed that this activity has been of critical importance in the discovery of trazodone. In fact, the development of this drug was based on the working hypothesis that a disturbance in the perception of unpleasant experience has a role in the pathogenesis of depression. Some medical implications of the α-blocking activity of trazodone are discussed. Trazodone is preferable to other antidepressant treatment when depression is associated with angle-closure glaucoma, cardiovascular disturbances depending on noradrenaline release, tremor, some psychotic conditions and alcoholism.

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A Possible Mechanism of Central Action of Trazodone in Rats

Cited by 10 publications

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Responses to tyramine and norepinephrine after imipramine and trazodone

Responses to tyramine and norepinephrine after imipramine and trazodone

Evaluating the dose-dependent mechanism of action of trazodone by estimation of occupancies for different brain neurotransmitter targets

Trazodone, a New Avenue in the Treatment of Depression

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