The pharmacokinetic profile of synthetic cathinones in a pregnancy model

Strange, Lauren G.; Kochelek, Kerri; Keasling, Robert; Brown, Stacy D.; Pond, Brooks B.

doi:10.1016/j.ntt.2017.08.001

Cited by 12 publications

(2 citation statements)

References 21 publications

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“…В метаболизме MДПВ наиболее важными являются изоферменты CYP2C19, CYP1A2 и CYP2D6. На втором этапе «соли» конъюгируются либо с глюкуроновой кислотой, либо с сульфатом [31,32]. Однако вследствие анатомофизиологических особенностей и незрелости изоферментов и ферментов печени это приводит к повышению концентрации синтетических наркотиков у внутриутробного ребенка по сравнению с кровью матери [33].…”

Section: Discussionunclassified

Pathophysiological mechanisms and clinical consequences of exposure to new psychoactive substances (“salts”) on a newborn

Loshkova,

Doroshenko,

Liulka

et al. 2024

Pediatr. farmakol.

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Background. The usage of new psychoactive substances (NPAS) is increasing every year among various social groups around the world. According to various authors, the use of abused drugs during pregnancy remains at a high level — from 2.8 to 7% of pregnant women. The usage of NPAS, as well as other groups of abused drugs, during pregnancy is fraught with intrauterine multi-organ damage, however, any organ and tissue specificity for NPAS has not been described. In intervention trials conducted on laboratory animals, negative pathophysiological mechanisms triggered by synthetic cathinones have been demonstrated in the form of increased proapoptotic activity, the formation of autophagolysosomes and reactive oxygen intermediates in cells of nervous tissue, and the pro-inflammatory orientation of cells of the immune system.Case report describes a predominant lesion of the nervous system (developmental brain malformations, damage to the inspiratory center) and the musculoskeletal system (pronounced miotonical syndrome, congenital pathological fractures of the femurs), leading to multiorgan dysfunction, uncontrolled inflammatory response and, as a result, to the development of severe disablement of such children and an increase in the cohort of palliative pediatric patients. In the article, the authors focus on the pathophysiological mechanisms of NPAS for a deeper and more holistic understanding of the pathological process occurring in the body, in order to form and improve the medical judgment of specialist doctors and cite their own clinical observation as an illustration of the consequences of using NPAS during pregnancy. The authors believe that this review describing the case report is valuable from the point of view of practical applicability both for clinicians of various fields and for researchers.Conclusion. In addition, it is necessary to pay attention to the fact that the use of NPAS is of great social and economic significance, the description of such clinical observations, as well as in vitro studies, is relevant, and the expansion of ideas about the short-term and long-term negative consequences of the use of NPAS should serve as an initiating stage for the development of rehabilitation strategies for these patients

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Section: Discussionunclassified

Pathophysiological mechanisms and clinical consequences of exposure to new psychoactive substances (“salts”) on a newborn

Loshkova,

Doroshenko,

Liulka

et al. 2024

Pediatr. farmakol.

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“…A recent study showed that in mice MDPV crosses the placental barrier and reaches higher concentration in fetal brain than the structurally similar mephedrone and methylone. In addition, MDPV has longer half-life in utero , which means prolonged drug exposure for the fetal brain (Strange et al, 2017 ). Even a single injection of 10 mg/kg of MDPV to 7-day-old mouse pups was followed 24 h later by neurodegeneration (enhanced apoptosis) in specific brain regions, including the striatum and nucleus accumbens (Ádám et al, 2014 ).…”

Section: Introductionmentioning

confidence: 99%

Gestational Exposure to the Synthetic Cathinone Methylenedioxypyrovalerone Results in Reduced Maternal Care and Behavioral Alterations in Mouse Pups

et al. 2018

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The member of synthetic cathinone family, methylenedioxypyrovalerone (MDPV), is a frequently used psychoactive drug of abuse. The objective of our study was to determine the effect of MDPV (administered from the 8th to the 14th day of gestation) on the behavior of neonatal and adolescent mice, as well as its effect on maternal care. We measured maternal care (pup retrieval test, nest building), locomotor activity (open field test), and motor coordination (grip strength test) of dams, whereas on pups we examined locomotor activity at postnatal day 7 and day 21 (open field test) and motor coordination on day 21 (grip strength test). On fresh-frozen brain samples of the dams we examined the expression of two important peptides implicated in the regulation of maternal behavior and lactation: tuberoinfundibular peptide 39 (TIP39) mRNA in the thalamic posterior intralaminar complex, and amylin mRNA in the medial preoptic nucleus. We detected decreased birth rate and survival of offspring, and reduced maternal care in the drug-treated animals, whereas there was no difference between the motility of treated and control mothers. Locomotor activity of the pups was increased in the MDPV treated group both at 7 and 21 days of age, while motor coordination was unaffected by MDPV treatment. TIP39 and amylin were detected in their typical location but failed to show a significant difference of expression between the drug-treated and control groups. The results suggest that chronic systemic administration of the cathinone agent MDPV to pregnant mice can reduce birth rate and maternal care, and it also enhances motility (without impairment of motor coordination) of the offspring.

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Target Analysis of NPS in Other Alternative Matrices: Dried Blood Spots and Meconium

Morini¹,

Carelli²,

Moretti³

2022

Methods in Pharmacology and Toxicology

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The pharmacokinetic profile of synthetic cathinones in a pregnancy model

Cited by 12 publications

References 21 publications

Pathophysiological mechanisms and clinical consequences of exposure to new psychoactive substances (“salts”) on a newborn

Pathophysiological mechanisms and clinical consequences of exposure to new psychoactive substances (“salts”) on a newborn

Gestational Exposure to the Synthetic Cathinone Methylenedioxypyrovalerone Results in Reduced Maternal Care and Behavioral Alterations in Mouse Pups

Target Analysis of NPS in Other Alternative Matrices: Dried Blood Spots and Meconium

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