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Fa Yi Xue Za Zhi Aug 2021Synthetic cathinones are a class of new psychoactive substances with a structure similar to amphetamine drugs, which can produce excitatory effects similar to drugs such... (Review)
Review
Synthetic cathinones are a class of new psychoactive substances with a structure similar to amphetamine drugs, which can produce excitatory effects similar to drugs such as amphetamine and cocaine after being taken. In recent years, the abuse of synthetic cathinones worldwide has become increasingly serious, posing a serious threat to social security and public health. This article focuses on several common synthetic cathinones, collects their research results in animal autonomous activity experiments and drug dependence model experiments and summarizes their relevant experimental conclusions in animal body temperature regulation, learning and memory, and anxiety, in order to provide data reference and method guidance for the domestic development of related drug research.
Topics: Alkaloids; Amphetamine; Animals; Behavior, Animal; Illicit Drugs
PubMed: 34726012
DOI: 10.12116/j.issn.1004-5619.2021.310406 -
International Journal of Molecular... May 2019C-type natriuretic peptide (CNP) is an autocrine and paracrine mediator released by endothelial cells, cardiomyocytes and fibroblasts that regulates vital physiological... (Review)
Review
C-type natriuretic peptide (CNP) is an autocrine and paracrine mediator released by endothelial cells, cardiomyocytes and fibroblasts that regulates vital physiological functions in the cardiovascular system. These roles are conveyed via two cognate receptors, natriuretic peptide receptor B (NPR-B) and natriuretic peptide receptor C (NPR-C), which activate different signalling pathways that mediate complementary yet distinct cellular responses. Traditionally, CNP has been deemed the endothelial component of the natriuretic peptide system, while its sibling peptides, atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), are considered the endocrine guardians of cardiac function and blood volume. However, accumulating evidence indicates that CNP not only modulates vascular tone and blood pressure, but also governs a wide range of cardiovascular effects including the control of inflammation, angiogenesis, smooth muscle and endothelial cell proliferation, atherosclerosis, cardiomyocyte contractility, hypertrophy, fibrosis, and cardiac electrophysiology. This review will focus on the novel physiological functions ascribed to CNP, the receptors/signalling mechanisms involved in mediating its cardioprotective effects, and the development of therapeutics targeting CNP signalling pathways in different disease pathologies.
Topics: Atrial Natriuretic Factor; Cardiovascular System; Endothelial Cells; Ethanolamines; Humans; Myocardium; Myocytes, Cardiac; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Paracrine Communication; Phenethylamines; Receptors, Atrial Natriuretic Factor
PubMed: 31072047
DOI: 10.3390/ijms20092281 -
Biomedical Chromatography : BMC Jul 2023The purpose of this review study was to sum up the main recent advances reported in the scientific literature about the detection of common drugs of abuse in biological... (Review)
Review
The purpose of this review study was to sum up the main recent advances reported in the scientific literature about the detection of common drugs of abuse in biological samples upon their collection by dried blood spot devices. The most recent, innovative and fully validated methods for the qualitative and/or quantitative detection of common drugs of abuse are reported, including alprazolam, clonazepam, diazepam, 3,4-methylenedioxymethamphetamine, 3,4-methylenedioxyamphetamine, 3,4-methyl-enedioxyethylamphetamine, amphetamine, methamphetamine, cocaine, tetrahydrocannabinol, 6-monoacetylmorphine, morphine, codeine, hydromorphone, hydrocodone, oxycodone, noroxycodone, tramadol, methadone, buprenorphine, fentanyl, ketamine and their respective metabolites and γ-hydroxybutyric acid. Dried blood spot proved to be extremely promising for routine analysis of forensic cases, although large-scale experiments on real samples need to be performed to confirm the emerging advantages of the technique and remove the potential limitations still affecting its widespread application.
Topics: Tandem Mass Spectrometry; Substance Abuse Detection; Codeine; Methamphetamine; Amphetamine
PubMed: 36417316
DOI: 10.1002/bmc.5555 -
ELife Jul 2021The development of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) has been a critical in vitro advance in the study of patient-specific physiology,...
The development of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) has been a critical in vitro advance in the study of patient-specific physiology, pathophysiology, and pharmacology. We designed a new deep learning multitask network approach intended to address the low throughput, high variability, and immature phenotype of the iPSC-CM platform. The rationale for combining translation and classification tasks is because the most likely application of the deep learning technology we describe here is to translate iPSC-CMs following application of a perturbation. The deep learning network was trained using simulated action potential (AP) data and applied to classify cells into the drug-free and drugged categories and to predict the impact of electrophysiological perturbation across the continuum of aging from the immature iPSC-CMs to the adult ventricular myocytes. The phase of the AP extremely sensitive to perturbation due to a steep rise of the membrane resistance was found to contain the key information required for successful network multitasking. We also demonstrated successful translation of both experimental and simulated iPSC-CM AP data validating our network by prediction of experimental drug-induced effects on adult cardiomyocyte APs by the latter.
Topics: Action Potentials; Algorithms; Cell Differentiation; Computer Simulation; Deep Learning; ERG1 Potassium Channel; Electrophysiologic Techniques, Cardiac; Electrophysiological Phenomena; Gene Expression Regulation; Humans; Induced Pluripotent Stem Cells; Models, Biological; Myocytes, Cardiac; Phenethylamines; Sulfonamides
PubMed: 34212860
DOI: 10.7554/eLife.68335 -
Indian Heart Journal 2014Dofetilide is an effective antiarrhythmic agent for conversion of atrial fibrillation and atrial flutter as well as maintenance of sinus rhythm in appropriately selected... (Review)
Review
Dofetilide is an effective antiarrhythmic agent for conversion of atrial fibrillation and atrial flutter as well as maintenance of sinus rhythm in appropriately selected patients. However, as with other antiarrhythmic agents, proarrhythmia is a known adverse effect. The risk of dofetilide induced torsade de pointes (Tdp) is low when used with strict dosing criteria guided by renal function, QT interval and concomitant drug therapy. Benefit from dofetilide use must be individualized and weighed against the side effects and the role of other available treatment options. In this review, we discuss the underlying mechanism, risk factors and precautionary measures to avoid dofetilide induced QT prolongation and ventricular tachycardia/Tdp. We suggest a scheme for the management of QT prolongation, ventricular arrhythmia and Tdp as well.
Topics: Anti-Arrhythmia Agents; Electrocardiography; Humans; Phenethylamines; Risk Factors; Sulfonamides; Torsades de Pointes
PubMed: 25634399
DOI: 10.1016/j.ihj.2013.12.021 -
European Neuropsychopharmacology : the... Jun 20223,4-methylenedioxyamphetamine (MDA) is a psychoactive compound chemically related to the entactogen MDMA. MDA shares some of the entactogenic effects of MDMA but also...
3,4-methylenedioxyamphetamine (MDA) is a psychoactive compound chemically related to the entactogen MDMA. MDA shares some of the entactogenic effects of MDMA but also exerts stimulant effects and psychedelic properties at higher doses. Here, we examined the pharmacological properties of MDA analogs and related amphetamine-based compounds detected in street drug samples or in sport supplements. We examined the key pharmacological mechanisms including monoamine uptake inhibition and release using human embryonic kidney 293 cells stably transfected with the respective human transporters. Additionally, we assessed monoamine transporter and receptor binding and activation properties. MDA, its fluorinated analogs, as well as the α-ethyl containing BDB and the dimeric amphetamine DPIA inhibited NET with the greatest potency and preferentially inhibited 5-HT vs. dopamine uptake. The β‑methoxy MDA analog 3C-BOH and the amphetamine-based N,α-DEPEA inhibited NET and preferentially inhibited dopamine vs. 5-HT uptake. The test drugs mediated efflux of at least one monoamine with the exception of DPIA. Most compounds bound to 5-HT and 5-HT receptors (K ≤ 10 µM) and several substances activated the 5-HT and 5-HT receptor as partial or full agonists. Furthermore, several compounds interacted with adrenergic receptors and the trace amine-associated receptor 1 (TAAR1) in the micromolar range. The pharmacological profiles of some fluorinated and nonfluorinated MDA analogs resemble the profile of MDMA. In contrast, 3C-BOH and N,α-DEPEA displayed more pronounced dopaminergic activity similar to amphetamine. Pharmacokinetics and pharmacodynamics studies are necessary to better establish the risks and therapeutic potential of the tested drugs.
Topics: 3,4-Methylenedioxyamphetamine; Amphetamine; Carrier Proteins; Dopamine; Humans; Methamphetamine; N-Methyl-3,4-methylenedioxyamphetamine; Serotonin
PubMed: 35378384
DOI: 10.1016/j.euroneuro.2022.03.006 -
Drug Design, Development and Therapy 2015Several studies have shown that lisdexamfetamine (LDX) is efficacious in children and adolescents with attention-deficit/hyperactivity disorder (ADHD). (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
Several studies have shown that lisdexamfetamine (LDX) is efficacious in children and adolescents with attention-deficit/hyperactivity disorder (ADHD).
OBJECTIVES
Aims of this study were to systematically review the efficacy, acceptability, and tolerability of LDX in child and adolescent ADHD. Any randomized controlled trials (RCTs) of LDX versus placebo carried out in children and adolescents with ADHD were included.
DATA SOURCES
The searches of the SCOPUS, MEDLINE, CINAHL and Cochrane Controlled Trials Register were performed in September 2014. Additional searches in the ClinicalTrials. gov and EU Clinical Trials Register database were conducted.
STUDY ELIGIBILITY CRITERIA PARTICIPANTS AND INTERVENTIONS
This review included all RCTs of LDX versus placebo which were carried out in children and adolescents up to 18 years old. Additionally, the included studies must have reported the final outcomes of: i) severity of ADHD symptoms with standardized scales, ii) rates of improvement, iii) rates of discontinuation. To be more thorough, the languages of such RCTs were not limited.
STUDY APPRAISAL AND SYNTHESIS METHODS
The abstracts from databases were inspected and the full text versions of relevant trials were examined and extracted for important outcomes. The efficacious measurements included either the pooled mean end-point or changed scores of ADHD rating scales, and the rate of improvement. Acceptability and tolerability were measured by the pooled overall discontinuation rate and the pooled discontinuation rate due to adverse events, respectively. A random effect model technique was utilized to synthesize the mean differences (either standardized mean differences or weighted mean differences) and relative risks (RRs) with 95% confidence intervals (CIs).
RESULTS
A total of 1,016 children and adolescents with ADHD were included. The dosage of LDX was 30 to 70 mg/day. The pooled mean change scores of LDX-treated group was significantly greater than that of the placebo (weighted mean difference [95% CI] of -15.20 [-19.95, -10.46], I (2)=94%). The pooled improvement rate of the LDX-treated group was also significantly higher than that of the placebo (RR [95% CI] of 0.34 [0.24, 0.47], I (2)=80%). The pooled overall discontinuation rate between the two groups was not significantly different (RR [95% CI] of 0.78 [0.46, 1.31], I (2)=63%). Similarly, the pooled discontinuation rate due to adverse events between the two groups showed no significant difference (RR [95% CI] of 1.99 [0.70, 5.64], I (2)=0%).
LIMITATIONS
The number of included studies was limited (five RCTs).
CONCLUSION
According to the present review, LDX was effective and well-tolerated in the treatment of child and adolescent ADHD. Unfortunately, the acceptability of LDX was not better than the placebo. Since the number of included studies was limited, the outcome from this review should be carefully interpreted and considered as preliminary. Further studies, therefore, should be conducted to confirm these findings.
IMPLICATION OF KEY FINDINGS
Lisdexamfetamine is an efficacious stimulant for treating child and adolescent ADHD.
Topics: Adolescent; Attention Deficit Disorder with Hyperactivity; Child; Drug Tolerance; Humans; Lisdexamfetamine Dimesylate; Randomized Controlled Trials as Topic
PubMed: 25897203
DOI: 10.2147/DDDT.S79071 -
ACS Chemical Neuroscience Aug 2023Serotonergic psychedelics are described to have activation of the serotonin 2A receptor (5-HT) as their main pharmacological action. Despite their relevance, the...
Serotonergic psychedelics are described to have activation of the serotonin 2A receptor (5-HT) as their main pharmacological action. Despite their relevance, the molecular mechanisms underlying the psychedelic effects induced by certain 5-HT agonists remain elusive. One of the proposed hypotheses is the occurrence of biased agonism, defined as the preferential activation of certain signaling pathways over others. This study comparatively monitored the efficiency of a diverse panel of 4-position-substituted (and -benzyl-derived) phenylalkylamines to induce recruitment of β-arrestin2 (βarr2) or miniGα to the 5-HT, allowing us to assess structure-activity relationships and biased agonism. All test compounds exhibited agonist properties with a relatively large range of both EC and values. Interestingly, the lipophilicity of the 2C-X phenethylamines was correlated with their efficacy in both assays but yielded a stronger correlation in the miniGα- than in the βarr2-assay. Molecular docking suggested that accommodation of the 4-substituent of the 2C-X analogues in a hydrophobic pocket between transmembrane helices 4 and 5 of 5-HT may contribute to this differential effect. Aside from previously used standard conditions (lysergic acid diethylamide (LSD) as a reference agonist and a 2 h activation profile to assess a compound's activity), serotonin was included as a second reference agonist, and the compounds' activities were also assessed using the first 30 min of the activation profile. Under all assessed circumstances, the qualitative structure-activity relationships remained unchanged. Furthermore, the use of two reference agonists allowed for the estimation of both "benchmark bias" (relative to LSD) and "physiology bias" (relative to serotonin).
Topics: Serotonin; Receptor, Serotonin, 5-HT2A; Molecular Docking Simulation; Hallucinogens; Phenethylamines; Serotonin 5-HT2 Receptor Agonists
PubMed: 37474114
DOI: 10.1021/acschemneuro.3c00267 -
Molecules (Basel, Switzerland) Nov 2020Amaryllidaceae are bulbous wild and cultivated plants well known for their beautiful flowers and pharmaceutical applications, essentially due to the alkaloids and... (Review)
Review
Amaryllidaceae are bulbous wild and cultivated plants well known for their beautiful flowers and pharmaceutical applications, essentially due to the alkaloids and flavonoids content. Hundreds of alkaloids have been isolated until now and several scientific publications reported their sources, chemical structures, and biological activities. During the last decade, some unstudied Amaryllidaceae plants were the object of in-depth investigations to isolate and chemically and biologically characterize new and already known alkaloids as well as some analogues. This review describes the isolation and chemical and biological characterization of the Amaryllidaceae alkaloids, and their analogues obtained in the last decade, focusing the discussion on the new ones.
Topics: Amaryllidaceae; Amaryllidaceae Alkaloids; Medicine, Traditional; Phytotherapy; Plant Extracts; Plant Roots; Structure-Activity Relationship
PubMed: 33260413
DOI: 10.3390/molecules25235621 -
Biomedicine & Pharmacotherapy =... Jun 2022We investigated the protective effects of ephedra herb (HEPH) on adriamycin-induced testicular toxicity in rats and explored the potential mechanisms underlying these...
OBJECTIVE
We investigated the protective effects of ephedra herb (HEPH) on adriamycin-induced testicular toxicity in rats and explored the potential mechanisms underlying these effects.
METHODS
A rat model of adriamycin injury was established, and sperm motility-related indicator and oxidative stress levels in the testis were evaluated. Serum levels of sex hormones and levels of testicular cell apoptosis were detected by enzyme-linked immunosorbent assay and flow cytometry, respectively. Western blotting (WB), immunofluorescence analyses, and reverse transcription-polymerase chain reaction (RT-PCR) were performed to evaluate the gonadotropin-releasing hormone (GnRH) signalling pathway- and meiosis-related genes and proteins. In subsequent in vitro experiments, adriamycin was used to stimulate GC-1 cells, which were treated with HEPH, ephedrine, or pseudoephedrine. Cell viability was assessed using flow cytometry to detect apoptosis and reactive oxygen species, whereas the GnRH signalling pathway and levels of meiosis-related genes and proteins were evaluated by InCell WB, a high-content imaging system, and RT-PCR.
RESULTS
Per in vivo experiments, HEPH restored testicular weight and function, sperm characteristics, serum and tissue hormonal levels, and antioxidant defences and significantly activated the GnRH signalling pathway- and meiosis-related protein levels. All protective effects of HEPH against adriamycin-induced injury were antagonised by the GnRH antagonist cetrorelix. In vitro, HEPH, ephedrine, and pseudoephedrine significantly reduced adriamycin-induced GC-1 cell apoptosis and reactive oxygen species levels and increased the expression of GnRH signalling pathway- and meiosis-related proteins. The effect of pseudoephedrine was greater than that of ephedrine, and these findings may be an important basis for understanding the effects of HEPH.
Topics: Animals; Doxorubicin; Ephedra; Ephedrine; Gonadotropin-Releasing Hormone; Male; Pseudoephedrine; Rats; Reactive Oxygen Species; Sperm Motility; Testis
PubMed: 35658231
DOI: 10.1016/j.biopha.2022.113061