Abnormal pregnancy outcome associated with high-dose maternal tranylcypromine therapy: Case report and literature review

Kennedy, Debra; Webster, William S.; Hill, Majella; Ritchie, Helen E.

doi:10.1016/j.reprotox.2017.02.012

Cited by 8 publications

(4 citation statements)

References 24 publications

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“…Tranylcypromine (2-PCPA, Parnate), one of nonselective and irreversible MAO-A/MAO-B inhibitors (MAOIs), is used to treat refractory depression after many other drugs have failed to treat the symptoms ( 3 ). The common side effects of tranylcypromine are sleep disturbances, orthostatic or postural hypotension, hallucinations, fatigue, blurred vision, headache, and gastrointestinal discomfort and disorders ( 3 , 23 , 24 ). Although with little evidence at the molecular and cellular levels, high-dose tranylcypromine may cause brain damage and inhibit brain development ( 25 – 27 ).…”

Section: Introductionmentioning

confidence: 99%

Tranylcypromine Causes Neurotoxicity and Represses BHC110/LSD1 in Human-Induced Pluripotent Stem Cell-Derived Cerebral Organoids Model

et al. 2017

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Recent breakthroughs in human pluripotent stem cell-derived cerebral organoids provide a valuable platform for investigating the human brain after different drugs treatments and for understanding the complex genetic background to human pathology. Here, we identified tranylcypromine, which is used to treat refractory depression, caused human-induced pluripotent stem cell-derived brain organoids neurotoxicity, leading to decreased proliferation activity and apoptosis induction. Moreover, tranylcypromine treatment affects neurons and astrocytes, which impairs cell density and arrangement. Finally, staining of histone demethylation-related genes revealed that tranylcypromine suppresses the transcriptional activity of BHC110/LSD1-targeted genes and increases the expression of histone di-methylated K4. These results show that human brain organoids can be applied as an in vitro model for CNS drug screening to evaluate structural, cellular, and molecular changes in the normal brains or brains of patients with neuropsychiatric disorders after drug treatments.

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Section: Introductionmentioning

confidence: 99%

Tranylcypromine Causes Neurotoxicity and Represses BHC110/LSD1 in Human-Induced Pluripotent Stem Cell-Derived Cerebral Organoids Model

et al. 2017

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“…Abnormal pregnancy outcome including fetal death and dysmorphism is associated with high-dose maternal TCP therapy. 137 The poisoning was described for 35 cases with TCP usage and 56 cases with usage of MAOI phenelzine, which is one of the few non-selective and irreversible MAOIs still in widespread clinical use. 138 Sixty to 75 seconds after intravenous injection of non-convulsive dose of tryptamine (5 mg/kg), brain concentration of the amine tryptamine was increased 5.4-fold.…”

Section: Resultsmentioning

confidence: 99%

Diet-Related Metabolic Perturbations of Gut Microbial Shikimate Pathway-Tryptamine-tRNA Aminoacylation-Protein Synthesis in Human Health and Disease

Paley

2019

Int J�Tryptophan�Res

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Human gut bacterial Na(+)-transporting NADH:ubiquinone reductase (NQR) sequence is associated with Alzheimer disease (AD). Here, Alzheimer disease-associated sequence (ADAS) is further characterized in cultured spore-forming Clostridium sp. Tryptophan and NQR substrate ubiquinone have common precursor chorismate in microbial shikimate pathway. Tryptophan-derived tryptamine presents in human diet and gut microbiome. Tryptamine inhibits tryptophanyl-tRNA synthetase (TrpRS) with consequent neurodegeneration in cell and animal models. Tryptophanyl-tRNA synthetase inhibition causes protein biosynthesis impairment similar to that revealed in AD. Tryptamine-induced TrpRS gene-dose reduction is associated with TrpRS protein deficiency and cell death. In animals, tryptamine treatment results in toxicity, weight gain, and prediabetes-related hypoglycemia. Sequence analysis of gut microbiome database reveals 89% to 100% ADAS nucleotide identity in American Indian (Cheyenne and Arapaho [C&A]) Oklahomans, of which ~93% being overweight or obese and 50% self-reporting type 2 diabetes (T2D). Alzheimer disease-associated sequence occurs in 10.8% of C&A vs 1.3% of healthy American population. This observation is of considerable interest because T2D links to AD and obesity. Alzheimer disease-associated sequence prevails in gut microbiome of colorectal cancer, which linked to AD. Metabolomics revealed that tryptamine, chorismate precursor quinate, and chorismate product 4-hydroxybenzoate (ubiquinone precursor) are significantly higher, while tryptophan-containing dipeptides are lower due to tRNA aminoacylation deficiency in C&A compared with non-native Oklahoman who showed no ADAS. Thus, gut microbial tryptamine overproduction correlates with ADAS occurrence. Antibiotic and diet additives induce ADAS and tryptamine. Mitogenic/cytotoxic tryptamine cause microbial and human cell death, gut dysbiosis, and consequent disruption of host-microbe homeostasis. Present analysis of 1246 participants from 17 human gut metagenomics studies revealed ADAS in cell death diseases.

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“…However, details on the outcomes of the pregnancies involving tranylcypromine were not reported. In two abnormal children born to a woman on tranylcypromine (100-120 mg/day), placental infarcts and congenital anomalies were attributed to a reduction in uteroplacental blood flow [75].…”

Section: • Tranylcyprominementioning

confidence: 98%

“…The Collaborative Perinatal Project reported increased malformations among 21 mother-child pairs exposed to monoamine oxidase inhibitors during the first trimester [75]. Tranylcypromine was used in 13 of these cases.…”

Section: • Tranylcyprominementioning

confidence: 99%

Depression Treatment in Pregnancy: Is It Safe, or Is It Not?

Gallitelli,

Franco,

Guidi

et al. 2024

IJERPH

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Prenatal depression carries substantial risks for maternal and fetal health and increases susceptibility to postpartum depression. Untreated depression in pregnancy is correlated with adverse outcomes such as an increased risk of suicidal ideation, miscarriage and neonatal growth problems. Notwithstanding concerns about the use of antidepressants, the available treatment options emphasize the importance of specialized medical supervision during gestation. The purpose of this paper is to conduct a brief literature review on the main antidepressant drugs and their effects on pregnancy, assessing their risks and benefits. The analysis of the literature shows that it is essential that pregnancy be followed by specialized doctors and multidisciplinary teams (obstetricians, psychiatrists and psychologists) who attend to the woman’s needs. Depression can now be treated safely during pregnancy by choosing drugs that have no teratogenic effects and fewer side effects for both mother and child. Comprehensive strategies involving increased awareness, early diagnosis, clear guidelines and effective treatment are essential to mitigate the impact of perinatal depression.

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Abnormal pregnancy outcome associated with high-dose maternal tranylcypromine therapy: Case report and literature review

Cited by 8 publications

References 24 publications

Tranylcypromine Causes Neurotoxicity and Represses BHC110/LSD1 in Human-Induced Pluripotent Stem Cell-Derived Cerebral Organoids Model

Tranylcypromine Causes Neurotoxicity and Represses BHC110/LSD1 in Human-Induced Pluripotent Stem Cell-Derived Cerebral Organoids Model

Diet-Related Metabolic Perturbations of Gut Microbial Shikimate Pathway-Tryptamine-tRNA Aminoacylation-Protein Synthesis in Human Health and Disease

Depression Treatment in Pregnancy: Is It Safe, or Is It Not?

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