Comparative Cardiovascular Toxicity of Trazodone and Imipramine in the Rat

Campana, A.; Barcellona, P. Scorza

doi:10.1007/978-3-642-66896-8_23

Cited by 10 publications

(4 citation statements)

References 2 publications

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“…It is known that oxidative stress cause disorders such as myocardial hypertrophy, contractile dysfunction, development of interstitial cardiac fibrosis, and endothelial dysfunction. [70][71][72][73] In the heart, reactive oxygen species are produced during normal cellular functions of mitochondria during oxidative phosphorylation as well as enzymatic reactions catalyzed by xanthine oxidase, NAD(P)H oxidases, and cytochrome P450. 74 Additionally, oxidative stress is also induced with reactive metabolites which are formed via phase I biotransformation reactions after drug exposure in the heart.…”

Section: Discussionmentioning

confidence: 99%

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Assessment of trazodone-induced cardiotoxicity after repeated doses in rats

et al. 2018

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Trazodone (TRZ) is an antidepressant drug commonly used in the treatment of depression, anxiety, and insomnia. Although some studies demonstrated the adverse effects of TRZ related to cardiovascular system, the conflicting results were observed in these studies. Therefore, we aimed to investigate the cardiac adverse effects of TRZ in rats at repeated doses in our study. In accordance with this purpose, TRZ was administered orally to rats at 5, 10, and 20 mg/kg doses for 28 days. Electrocardiogram records, serum aspartate aminotransferase (AST), lactate dehydrogenase, creatine kinase-myoglobin band, cardiac troponin-T (cTn-T) levels, DNA damage in cardiomyocytes, and histologic view of heart tissues were evaluated. In addition, glutathione (GSH) and malondialdehyde (MDA) levels were measured to determine the oxidative status of cardiac tissue after TRZ administration. Heart rate was decreased, PR interval was prolonged, and QRS and T amplitudes were decreased in 20 mg/kg TRZ-administered group compared to the control group. Serum AST and cTn-T levels were significantly increased in 10 and 20 mg/kg TRZ-administered rats with respect to control rats. DNA damage was significantly increased in these groups. Additionally, degenerative histopathologic findings were observed in TRZ-administered groups. Although there was no difference in MDA levels between groups, GSH levels were significantly decreased in 10 and 20 mg/kg TRZ-administered groups compared to the control group. Our results have shown that TRZ induced cardiotoxicity in rats dose-dependently. It is assumed that oxidative stress related to GSH depletion may be accompanied by these adverse effects.

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Section: Discussionmentioning

confidence: 99%

“…GSH depletion is considered as an indicator of oxidative stress in the heart tissue. 72,[75][76][77] Similar to GSH depletion, increasing MDA levels, which is an end product of lipid peroxidation, in the heart tissue also indicates oxidative stress. After myocardial ischemia, increase of MDA levels in the heart was established.…”

Section: Discussionmentioning

confidence: 99%

Assessment of trazodone-induced cardiotoxicity after repeated doses in rats

et al. 2018

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“…In the early 1970s, while concerns about the side effects of MAOIs and TCAs were being developed, evidence for the function of serotonin in depression was growing. This has sparked an era of novel antidepressants [ 36 , 37 ]. In this regard, researchers have attempted to discover compounds that may selectively inhibit serotonin reuptake without cardiotoxicity or anticholinergic effects of TCAs [ 38 ].…”

Section: Main Subjectsmentioning

confidence: 99%

The Role of Glutamate Underlying Treatment-resistant Depression

Kim

Lee

et al. 2023

Clin Psychopharmacol Neurosci

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The monoamine hypothesis has significantly improved our understanding of mood disorders and their treatment by linking monoaminergic abnormalities to the pathophysiology of mood disorders. Even 50 years after the monoamine hypothesis was established, some patients do not respond to treatments for depression, including selective serotonin reuptake drugs. Accumulating evidence shows that patients with treatment-resistant depression (TRD) have severe abnormalities in the neuroplasticity and neurotrophic factor pathways, indicating that different treatment approaches may be necessary. Therefore, the glutamate hypothesis is gaining attention as a novel hypothesis that can overcome monoamine restrictions. Glutamate has been linked to structural and maladaptive morphological alterations in several brain areas associated with mood disorders. Recently, ketamine, an N-methyl-D-aspartate receptor (NMDAR) antagonist, has shown efficacy in TRD treatment and has received the U.S. Food and Drug Administration approval, revitalizing psychiatry research. However, the mechanism by which ketamine improves TRD remains unclear. In this review, we re-examined the glutamate hypothesis, bringing the glutamate system onboard to join the modulation of the monoamine systems, emphasizing the most prominent ketamine antidepressant mechanisms, such as NMDAR inhibition and NMDAR disinhibition in GABAergic interneurons. Furthermore, we discuss the animal models used in preclinical studies and the sex differences in the effects of ketamine.

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“…In some respects, trazodone resembles both the benzodiaze pines and the antipsychotic drugs; it causes sedation and depresses rapid eye movement (REM) sleep [3]. Like the phenothiazines, it suppresses self-stimulation behavior and amphetamine actions and produces quite marked adrenergic blockade [4], Unlike the phenothiazines and almost all other antide pressants, it has minimal anticholinergic ef fects [5], As we showed 10 years ago, the EEG effects produced by trazodone differ from those of imipramine [6], and trazo done is less likely to induce adverse cardiac effects [7], In a comprehensive independent review of trazodone in 1981. Brogden et al [8] con cluded that trazodone 'has an overall thera peutic efficacy comparable with imipramine and amitriptyline in depressive illness'; it 'causes fewer anticholinergic side effects than the tricyclic antidepressants'; it 'ap pears also to have activity against the con comitant anxiety in depressed patients'; it 'is less likely than imipramine to cause cardio toxicity at therapeutic doses'; the 'effects of overdosage are not known at present'; and trazodone 'appears to be well tolerated by the elderly'.…”

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confidence: 99%

Recent Experience with Trazodone

Lader¹

1987

Psychopathology

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Trazodone is an atypical antidepressant with additional anxiolytic effects. Recent European experience with trazodone is reviewed with respect to antidepressant efficacy, side effects (particularly anticholinergic), anxiolytic actions, cardiotoxicity, overdosage, and use in the elderly. From the data presented in this paper it is concluded that trazodone is effective both as an antidepressant and as an anxiolytic agent, with few side effects and low cardiotoxicity. It is safer than tricyclic antidepressant agents in overdosage and better tolerated in the elderly patient.

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Comparative Cardiovascular Toxicity of Trazodone and Imipramine in the Rat

Cited by 10 publications

References 2 publications

Assessment of trazodone-induced cardiotoxicity after repeated doses in rats

Assessment of trazodone-induced cardiotoxicity after repeated doses in rats

The Role of Glutamate Underlying Treatment-resistant Depression

Recent Experience with Trazodone

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