RESUMO
Intellectual drug doping in athletics by using stimulants that affect central nervous system functions has been diversified. Stimulants are regulated by the World Anti-Doping Agency according to their levels of urinary concentration. Positron emission tomography could evaluate how stimulants affect central nervous system functions. We aimed to evaluate the effect of stimulants on brain function by examining the difference in brain dopamine transporter occupancy by PET after administration of dl-methylephedrine or pseudoephedrine at the clinical maximum daily dose. Four PET scans without and with drug administration (placebo, dl-methylephedrine 150 mg and pseudoephedrine 240 mg) were performed. The concentrations of dl-methylephedrine and pseudoephedrine in plasma and urine were measured. DAT occupancies in the striatum with placebo, dl-methylephedrine and pseudoephedrine were calculated by PET images. The urinary concentration of dl-methylephedrine (12.7 µg/mL) exceeded the prohibited concentration (10 µg/mL), but the DAT occupancy with dl-methylephedrine (6.1%) did not differ (p = 0.92) from that with placebo (6.2%). By contrast, although the urinary concentration of pseudoephedrine (144.8 µg/mL) was below the prohibited concentration (150 µg/mL), DAT occupancy with pseudoephedrine was 18.4%, which was higher than that with placebo (p = 0.009). At the maximum clinical dose, dl-methylephedrine was shown to have weaker effects on brain function than pseudoephedrine.
Assuntos
Encéfalo , Proteínas da Membrana Plasmática de Transporte de Dopamina , Tomografia por Emissão de Pósitrons , Pseudoefedrina , Humanos , Masculino , Tomografia por Emissão de Pósitrons/métodos , Pseudoefedrina/farmacologia , Pseudoefedrina/administração & dosagem , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/diagnóstico por imagem , Adulto , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Adulto Jovem , Estimulantes do Sistema Nervoso Central/farmacologia , Estimulantes do Sistema Nervoso Central/urina , Estimulantes do Sistema Nervoso Central/administração & dosagem , Dopagem Esportivo/prevenção & controle , Feminino , Efedrina/análogos & derivadosRESUMO
OBJECTIVE: To assess the impact of ejaculatory dysfunction (EjD; failure of emission or retrograde ejaculation) on health-related quality of life (HRQoL) after retroperitoneal lymph node dissection (RPLND) for testicular cancer and explore the efficacy of pseudoephedrine hydrochloride as treatment. PATIENTS AND METHODS: In a single arm, phase II trial, patients at ≥6 months after RPLND were invited to complete patient-reported outcome measures (European Organisation for Research and Treatment of Cancer [EORTC] quality of life questionnaire [QLQ]-30-item core, EORTC QLQ-testicular cancer-26, and Brief Male Sexual Function Inventory) evaluating HRQoL and sexual function in follow-up (ACTRN12622000537752/12622000542796). If EjD was reported, post-ejaculatory urine ± semen analysis was undertaken. In eligible patients, pseudoephedrine hydrochloride 60 mg was administered orally every 6 h for six doses. The primary endpoint was sperm count >39 million sperm/ejaculate (>5th centile) following treatment. The trial was powered to detect a clinically relevant 36% achieving sperm count of >39 million sperm/ejaculate. Secondary endpoints included semen volume >1.5 mL, total motile sperm count, safety, and HRQoL impacts. RESULTS: Of the 58 patients enrolled, the median (interquartile range [IQR]) age was 35 (29-41) years, with a median (IQR) of 37 (18-60) months from RPLND. EjD was reported in 33 (57%), including 27/52 (52%) receiving follow-up at our centre. There were no differences in global HRQoL; however, role functioning (P = 0.045), sexual problems (P < 0.005), and sexual enjoyment (P = 0.005) was poorer if EjD was present. In all, 24/33 (73%) patients with EjD consented to pseudoephedrine treatment. Of 22 evaluable patients, four (18%) achieved a sperm count of >39 million/ejaculate (P = 0.20), and four (18%) had a semen volume of >1.5 mL (P = 0.20). There was a mean increase of 105 million sperm/ejaculate (P = 0.051) and 1.47 mL increase in semen volume (P = 0.01). No safety concerns arose. CONCLUSION: Ejaculatory dysfunction is common after RPLND but did not impact global HRQoL in our cohort. Pseudoephedrine improved EjD for some; however, its efficacy was lower than expected. Pseudoephedrine may be considered on an individualised basis.
Assuntos
Ejaculação , Excisão de Linfonodo , Pseudoefedrina , Qualidade de Vida , Disfunções Sexuais Fisiológicas , Neoplasias Testiculares , Masculino , Humanos , Neoplasias Testiculares/tratamento farmacológico , Neoplasias Testiculares/cirurgia , Adulto , Excisão de Linfonodo/efeitos adversos , Ejaculação/efeitos dos fármacos , Pseudoefedrina/efeitos adversos , Pseudoefedrina/uso terapêutico , Pseudoefedrina/administração & dosagem , Disfunções Sexuais Fisiológicas/etiologia , Disfunções Sexuais Fisiológicas/induzido quimicamente , Espaço Retroperitoneal , Pessoa de Meia-Idade , Medidas de Resultados Relatados pelo Paciente , Contagem de Espermatozoides , Disfunção EjaculatóriaRESUMO
Methamphetamine (MA) is one of the most virulent illicit drugs that can be synthesized from household materials leading to its prevalent trafficking and local manufacturing in clandestine drug laboratories (clan labs). The significant problems of tracing MA in clan labs and monitoring drug abusers lie in the lag time between sample collection and analysis and the number of tests done. Capillary electrophoresis (CE) is a rapid separation technique amenable to miniaturization and field testing. Herein, we developed a simple transient isotachophoretic (tITP)-CE method to detect MA and its precursor pseudoephedrine (PSE) in clan labs and non-invasive biological fluids. The method was implemented on the ETD-100, a commercial fully automated portable CE instrument with an integrated swab-based extraction system. Within 2 min of insertion of the swab, MA and PSE were automatically extracted with a leading electrolyte (LE) and then separated on covalently modified capillaries. The ETD-100 showed a limit of detection (LOD) and quantification (LOQ) of MA 0.02 and 0.05 µg/swab and 0.02 and 0.06 µg/swab of PSE, with an enhancement factor of 118 and 328, respectively, when compared to a normal non-tITP injection. The intra and inter-day relative standard deviation in terms of migration time were in the range of 0.75-1.93 % for both MA and PSE and were 2.0-2.4 % for both MA and PSE peak height. The method was demonstrated with the detection of spiked MA and PSE on different household materials as well as in non-invasive biological fluids with a recovery above 60 %.
Assuntos
Eletroforese Capilar , Metanfetamina , Metanfetamina/análise , Metanfetamina/isolamento & purificação , Eletroforese Capilar/métodos , Humanos , Limite de Detecção , Pseudoefedrina/análise , Pseudoefedrina/isolamento & purificação , Detecção do Abuso de Substâncias/métodos , Detecção do Abuso de Substâncias/instrumentação , Drogas Ilícitas/análise , Drogas Ilícitas/isolamento & purificaçãoRESUMO
BACKGROUND: There is an increasing interest of the scientific community in developing innovative methodologies for their analysis needs within a green analytical chemistry framework. UV spectrophotometry is one of the most promising eco-friendly methods, which is integrated with advanced chemometric tools to enhance the selectivity of the analysis of complex mixtures with severe overlapped signals. OBJECTIVE: Simultaneous determination of a triple-combination of pseudoephedrine hydrochloride (PSE), carbinoxamine maleate (CRX), and paracetamol (PAR) using an artificial intelligence system and multivariate calibration methods. This combination has been recently recommended for COVID-19 home-treated patients as part of a symptomatic treatment. METHODS: Namely, the suggested models are artificial neural networks, partial least-squares, and principal component regression. The proposed algorithms were optimized and developed with the aid of a five-level, three-factor experimental design. RESULTS: The investigated methods were applied over the concentration range of 100-180 µg/mL, 18-16 µg/mL, and 4-12 µg/mL for PSE, CRX, and PAR, respectively. The models' validation results demonstrated excellent recoveries (around 98 to 102%), signaling the approaches' outstanding resolution capacity for the cited compounds in the presence of common excipients. The outcomes of the studied methods were statistically compared to the official approaches, and no significant difference was found. CONCLUSIONS: The suggested models were efficiently employed to determine the selected drugs in their combined tablets without any initial separation steps. The impact of these methods on the environment was evaluated via greenness tools: namely, the National Environmental Method Index, Raynie and Driver's green assessment method, Analytical Eco-Scale, Green Analytical Procedure Index, and Analytical Greenness Metric. HIGHLIGHTS: Green chemometric quality assessment of PSE, CRX, and PAR in their pure and pharmaceutical dosage forms. The established approaches are innovative, sustainable, smart, fast, selective, and cost-effective. These models are potential green nominees for routine analysis of the investigated mixture in quality control laboratories.
Assuntos
Acetaminofen , Tratamento Farmacológico da COVID-19 , Combinação de Medicamentos , Acetaminofen/análise , Análise dos Mínimos Quadrados , Pseudoefedrina/análise , Redes Neurais de Computação , Química Verde/métodos , Análise de Componente Principal , Espectrofotometria Ultravioleta/métodos , Humanos , COVID-19 , Espectrofotometria/métodos , Algoritmos , SARS-CoV-2 , Quimiometria/métodos , PiridinasRESUMO
The use of controlled precursors for reaction optimisation is not always practical. One approach to limiting the use of controlled substances is to instead use 'model compounds'. Herein, two model compounds resembling norephedrine and ephedrine were selected based on their (i) structural similarity (i.e., presence of key functional groups) and (ii) availability from multiple suppliers without restriction. Model compounds 2-amino-1-phenylethanol and 2-(methylamino)-1-phenylethanol (halostachine), were compared to norephedrine and pseudoephedrine by firstly subjecting them to transformations known in the synthesis of amphetamines, and secondly, comparing the compounds using colourimetric spot tests, FTIR and NMR.
Assuntos
Anfetaminas , Estimulantes do Sistema Nervoso Central , Espectroscopia de Ressonância Magnética , Espectroscopia de Infravermelho com Transformada de Fourier , Anfetaminas/química , Estimulantes do Sistema Nervoso Central/química , Humanos , Efedrina/química , Colorimetria , Fenilpropanolamina/química , Pseudoefedrina/química , Modelos QuímicosRESUMO
Epimer separation is crucial in the field of analytical chemistry, separation science, and the pharmaceutical industry. No reported methods could separate simultaneously epimers or even isomers and remove other unwanted, co-existing, interfering substances from complex systems like herbal extracts. Herein, we prepared a heptapeptide-modified stationary phase for the separation of 1R,2S-(-)-ephedrine [(-)-Ephe] and 1S,2S-(+)-pseudoephedrine [(+)-Pse] epimers from Ephedra sinica Stapf extract and blood samples. The heptapeptide stationary phase was comprehensively characterized by scanning electron microscopy, X-ray photoelectron spectroscopy, and Fourier transform infrared spectroscopy. The separation efficiency of the heptapeptide column was compared with an affinity column packed with full-length ß2-AR functionalized silica gel (ß2-AR column). The binding affinity of the heptapeptide with (+)-Pse was 3-fold greater than that with (-)-Ephe. Their binding mechanisms were extensively characterized by chromatographic analysis, ultraviolet spectra, circular dichroism analysis, isothermal titration calorimetry, and molecule docking. An enhanced hydrogen bonding was clearly observed in the heptapeptide-(+)-Pse complex. Such results demonstrated that the heptapeptide can recognize (+)-Pse and (-)-Ephe epimers in a complex system. This work, we believe, was the first report to simultaneously separate epimers and remove non-specific interfering substances from complex samples. The method was potentially applicable to more challenging sample separation, such as chiral separation from complex systems.
Assuntos
Efedrina , Pseudoefedrina , Receptores Adrenérgicos beta 2 , Efedrina/química , Pseudoefedrina/química , Receptores Adrenérgicos beta 2/química , Receptores Adrenérgicos beta 2/metabolismo , Simulação de Acoplamento Molecular , Ephedra sinica/química , Cromatografia Líquida de Alta Pressão/métodos , Extratos Vegetais/química , Humanos , Estereoisomerismo , Oligopeptídeos/química , Oligopeptídeos/isolamento & purificaçãoRESUMO
This study examines purchasing patterns regarding oral decongestants, concerns about their efficacy, and the need for timelier postmarket evaluation.
Assuntos
Comércio , Fenilefrina , Pseudoefedrina , Comércio/tendências , Fenilefrina/economia , Fenilefrina/uso terapêutico , Pseudoefedrina/economia , Pseudoefedrina/uso terapêutico , Estados Unidos/epidemiologiaRESUMO
Methcathinone, a psychoactive substance with stimulant properties, has raised concerns in recent years due to its presence in urine screenings, even among individuals with no history of drug abuse. To prevent misjudgment, this work aims to explore the source of methcathinone in urine. A total of 58 urine samples tested positive for methcathinone in the National Taiwan University Hospital cohort, with 27 linked to illicit drug use and 31 from individuals with no drug use history. Co-occurrence analysis revealed a strong association between methcathinone and over-the-counter cold medications containing pseudoephedrine or ephedrine. In an in vivo experiment, participants who consumed pseudoephedrine-containing drugs showed the presence of methcathinone in their urine, suggesting a connection between these substances. Additionally, tests on pharmaceutical products containing pseudoephedrine detected small amounts of methcathinone as impurities. The findings suggest that the presence of methcathinone in nonillicit drug users may be attributed to impurities in over-the-counter pseudoephedrine-containing medications. This raises concerns about potential misinterpretations of drug screening results and underscores the need for more comprehensive criteria for assessing drug use. This study contributes to our understanding of the origin of methcathinone in urine, which has implications for legal justice and drug screening practices.
Assuntos
Líquidos Corporais , Propiofenonas , Transtornos Relacionados ao Uso de Substâncias , Humanos , Pseudoefedrina , Efedrina , Transtornos Relacionados ao Uso de Substâncias/diagnósticoRESUMO
ABSTRACT: Amphetamine derivatives are used worldwide legally or illegally and intoxications may be accompanied by cardiac arrhythmias. Here, we tested contractile effects of cumulative applied (±)-amphetamine, pseudoephedrine, nor-pseudoephedrine (cathine), and cathinone in electrically stimulated (1 Hz) human right atrial preparations (HAP) and mouse left atrial preparations and in spontaneously beating mouse right atrial preparations. In mouse atrial preparations, amphetamine increased force of contraction and beating rate in a concentration- and time-dependent manner, starting at 1 µM in left atrial preparations to 157.1% ± 3.0% and right atrial preparations to 146.6% ± 9.8% at 10 µM, respectively [mean ± standard error of the mean (SEM); n = 5; P < 0.05]. Pseudoephedrine, cathine, or cathinone alone were ineffective in mouse atrial preparations but after pre-incubation with the phosphodiesterase IV inhibitor rolipram (0.1 µM), a positive inotropic effect was noted (mean ± SEM: pseudoephedrine: 112.3% ± 9.8%; cathine: 109.0% ± 4.3%; cathinone: 138.3% ± 21.2%). The effects of all drugs were greatly attenuated by 10 µM cocaine or 10 µM propranolol treatments. However, In HAP, not only amphetamine (to a mean ± SEM of 208% ± 32%) but also pseudoephedrine (to a mean ± SEM of 287% ± 60%), cathine (to a mean ± SEM of 234% ± 52%), and cathinone (to a mean ± SEM of 217% ± 65%) increased force of contraction without the need of phosphodiesterase inhibition. The contractile effects in HAP were attenuated by 10 µM cocaine and antagonized by 10 µM propranolol. We conclude that amphetamine, pseudoephedrine, cathine, and cathinone act probably via release of noradrenaline from cardiac stores as indirect sympathomimetic agents in mouse and more pronounced in human atrial preparations.
Assuntos
Alcaloides , Anfetamina , Cocaína , Fenilpropanolamina , Humanos , Anfetamina/farmacologia , Pseudoefedrina/farmacologia , Propranolol/farmacologia , Contração MiocárdicaRESUMO
OBJECTIVES: The aetiology of gastroschisis is considered multifactorial. We conducted a systematic review and meta-analysis to assess whether the use of medications during pregnancy, is associated with the risk of gastroschisis in offspring. METHODS: PubMed, EMBASE, and Scopus were searched from 1st January 1990 to 31st December 2020 to identify observational studies examining the association between medication use during pregnancy and the risk of gastroschisis. The Newcastle-Ottawa Scale was used for the quality assessment of the individual studies. We pooled adjusted measures using a random-effect model to estimate relative risk [RR] and the 95% confidence interval [CI]. I2 statistic for heterogeneity and publication bias was calculated. RESULTS: Eighteen studies providing data on 751,954 pregnancies were included in the meta-analysis. Pooled RRs showed significant associations between aspirin (RR 1.66, 95% CI 1.16-2.38; I2 = 58.3%), oral contraceptives (RR 1.52, 95% CI 1.21-1.92; I2 = 22.0%), pseudoephedrine and phenylpropanolamine (RR 1.51, 95% CI 1.16-1.97; I2 = 33.2%), ibuprofen (RR 1.42, 95% CI 1.26-1.60; I2 = 0.0%), and gastroschisis. No association was observed between paracetamol and gastroschisis (RR 1.16, 95% CI 0.96-1.41; I2 = 39.4%). CONCLUSIONS: These results suggest that the exposure in the first trimester of pregnancy to over the counter medications (OTC) such as aspirin, ibuprofen, pseudoephedrine and phenylpropanolamine as well as to oral contraceptives, was associated with an increased risk of gastroschisis. However, these associations are significant only in particular subgroups defined by geographic location, adjustment variables and type of control. Therefore, further research is needed to investigate them as potential risk factors for gastroschisis, to assess their safety in pregnancy and to develop treatment strategies to reduce the risk of gastroschisis in offspring. PROSPERO registration number: CRD42021287529.
Assuntos
Gastrosquise , Feminino , Humanos , Gravidez , Aspirina , Anticoncepcionais Orais , Gastrosquise/epidemiologia , Gastrosquise/induzido quimicamente , Ibuprofeno , Fenilpropanolamina/efeitos adversos , Pseudoefedrina , Estudos Observacionais como AssuntoRESUMO
Pseudoephedrine (PSE) is an agent that is contained in common cold medications. The agent, which is used to treat cold and cough, is the fourth most prescribed drug group in some countries. During pregnancy, expectant mothers use PSE for colds and other reasons. One out of every four expectant mothers use PSE alone or in combination with other medicines for various reasons. This study was aimed to investigate effects of PSE on long bones development in rat during fetal growth. Pregnant rats were divided into five groups: control and four experimental groups (25 mg/kg, 50 mg/kg, 100 mg/kg, 200 mg/kg PSE). Between 1 and 20 days of pregnancy, PSE was given to them by gavage. Weights and heights of fetuses isolated by cesarean on the 21st day were measured. Ossification of femur and humerus was examined by three different methods mentioned earlier. Depending on the dose increase, all morphometric data, ossification rate and bone length of the fetuses were decreased. Besides, it was determined that the amount of Calcium in the bone tissue decreased in the analyzes made with SEM-EDX Analysis. The data obtained from this study reveal that the use of PSE during pregnancy disrupts the existing balance in the bone and negatively affects ossification due to the dose increase. In conclusion, we present descriptive and novel data on the effects of PSE use during pregnancy on the bone development of rat fetal long bones.
Assuntos
Osso e Ossos , Pseudoefedrina , Gravidez , Feminino , Ratos , Animais , Pseudoefedrina/farmacologia , Pseudoefedrina/uso terapêutico , Osteogênese , Feto , Desenvolvimento ÓsseoRESUMO
ISSUES: Project Stop, a real-time monitoring program for pseudoephedrine-containing medicines, was initiated in 2005 by the Pharmacy Guild of Australia in collaboration with police in the state of Queensland. The program implemented an online database to record pseudoephedrine purchases (and attempted purchases) to prevent large-scale diversion to methamphetamine production. APPROACH: This narrative review aims to understand the overall impact of Project Stop, what evidence exists for this kind of intervention in Australia, and what lessons can be learned from its introduction. Systematic database searches were conducted in Embase, PubMed, Web of Science and Google Scholar, with 20 relevant sources selected for inclusion. KEY FINDINGS: Project Stop successfully prevented some pseudoephedrine from being diverted from pharmacies to methamphetamine production. The intervention has been most effective in jurisdictions that made the program mandatory. Project Stop was also associated with a temporary decline in clandestine laboratory seizures in Queensland, changes in methamphetamine production methods and reduced voluntary treatment admissions for methamphetamine use. Implementation was not associated with an appreciable effect on secondary indicators, such as methamphetamine production and harmful use. IMPLICATIONS: Future applications of a Project Stop model must ensure ongoing impact evaluation, assessment of its effect on individual's drug-related behaviour and combine it with policies that address drug use as a health issue. CONCLUSION: Project Stop has been narrowly successful in terms of reducing pseudoephedrine diversion and demonstrates the potential for third-party policing practices directed at the consumer level, in collaboration with healthcare practitioners, rather than only regulating precursor wholesalers.
Assuntos
Metanfetamina , Farmácias , Transtornos Relacionados ao Uso de Substâncias , Humanos , Austrália , Pseudoefedrina , Transtornos Relacionados ao Uso de Substâncias/prevenção & controleRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: The stem of Musa paradisiaca (plantain) has found application in traditional medicine for the treatment of diabetes, inflammation, ulcers and wound injuries. AIM OF THE STUDY: This study investigated the phytochemical composition, toxicity profile, wound healing, anti-inflammatory and analgesic effects of aqueous Musa paradisiaca stem extract (AMPSE) in rats. METHODS: Phytochemical analysis of methanol-MPSE was performed by gas chromatography-mass spectrometry (GC-MS). Acute toxicity testing was carried out through oral administration of a single dose of AMPSE up to 5 g/kg. Four separate groups of rats were used for the subacute toxicity testing (n = 6). Group 1 served as a normal control and did not receive AMPSE, groups 2-4 received AMPSE daily by gavage for 28 days. In the experiments with excision and incision wounds, the rats were treated with 10 w/w AMPS extract. The anti-inflammatory and analgesic effects of AMPSE were assessed using egg albumin-induced paw oedema and acetic acid-induced writhing methods, respectively. For the subacute, anti-inflammatory and analgesic studies, AMPSE was administered to the experimental rats at doses of 300, 600 and 900 mg/kg body weight. RESULTS: Bioactive compounds identified include ß-sitisterol, n-hexadecanoic acid, octadecanoic acid, diethyl sulfate, p-hydroxynorephedrine, phenylephrine, nor-pseudoephedrine, metaraminol, pseudoephedrine and vanillic acid. No signs of toxicity and no deaths were observed in all the groups. For the groups treated with AMPSE for 28 days, a significant reduction in alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, urea, sodium, chloride, total cholesterol, triglycerides, and low-density lipoprotein cholesterol were observed while high density lipoprotein cholesterol, glutathione and superoxide dismutase increased compared to control (p < 0.05). In wound healing experiments, AMPSE showed greater percent wound contraction and wound resistance fracture compared to the povidone-iodine (PI) treated and control groups. Treatment with 900 mg/kg AMPSE resulted in significant (p < 0.05) anti-inflammatory and analgesic effects compared to the control. CONCLUSION: This study shows that AMPSE is not toxic but contains biologically active compounds with hepatoprotective, anti-inflammatory, lipid-lowering and wound-healing effects. Treatment of rats with AMPSE has shown that AMPSE has anti-inflammatory, analgesic, hepatoprotective, lipid-lowering and wound-healing effects, supporting its therapeutic use in ethnomedicine.
Assuntos
Musa , Musaceae , Plantago , Ratos , Animais , Musa/química , Extratos Vegetais/uso terapêutico , Extratos Vegetais/toxicidade , Pseudoefedrina/farmacologia , Analgésicos/uso terapêutico , Analgésicos/toxicidade , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/toxicidade , Cicatrização , Colesterol/farmacologia , Compostos Fitoquímicos/uso terapêutico , Compostos Fitoquímicos/toxicidade , Lipídeos/farmacologiaRESUMO
Ephedra herb, a dried terrestrial stem of Ephedra sinica, is used in traditional Japanese medicine (Kampo) and Chinese medicine to treat the common cold, headaches, bronchial asthma, and nasal inflammation. E. sinica predominantly contains two ephedrine alkaloids-(-)-ephedrine and (+)-pseudoephedrine-which are crucial for its medicinal effects. This study aimed to reveal the influence of genetic and environmental factors on ephedrine alkaloids content using statistical genetic analyses. To evaluate the influence of genetic factors on ephedrine alkaloids content, 25 clonal lines were cultivated in Ibaraki and the broad-sense heritability of the traits was estimated. The heritabilities of (-)-ephedrine, (+)-pseudoephedrine, and "total alkaloids" (TA) content were 0.871, 0.969, and 0.865, respectively. The heritabilities of ephedrine alkaloids content were high. To evaluate the influence of environmental factors on ephedrine alkaloids content, four clonal lines which have different genotypes were cultivated in three locations (Ibaraki, Shizuoka, and Yamanashi prefectures). The effects of genotype (G), location (L), and genotype by environment (G × E) interactions on ephedrine alkaloids content were found to be significant (p < 0.05) by two-way ANOVA, and, in particular, the genotypic effects were found to be the largest. Our results indicate that the ephedrine alkaloids content in E. sinica is under relatively strong genetic control and remains stable under various environments. These findings suggest that E. sinica with a higher and stable ephedrine alkaloids content could be cultivated in different locations through selective breeding.
Assuntos
Alcaloides , Medicamentos de Ervas Chinesas , Ephedra sinica , Efedrina , Ephedra sinica/genética , PseudoefedrinaRESUMO
Ephedra is one of the world's most important plants, used in medicine, plants and ecology. Most Ephedra grows in plain areas and is stable. But the plateau environment is special, with the change of altitude, the variety difference of plateau Ephedra saxatilis is very obvious. E. saxatilis metabolism on the Tibetan Plateau is not only affected by altitude, but also environmental conditions such as climate conditions and different soil components. However, the change mechanism of E. saxatilis alkaloids in special ecological environment is still unclear. Therefore, we analyzed the metabolic and altitude of E. saxatilis species in the Tibetan Plateau. Through the functional analysis of Kyoto Metabolism and Metabolomic Encyclopedia (KEGG), we can determine that the number of E. saxatilis metabolites decreases with the increase of altitude, and there are differences in metabolism among the three mountains. This was confirmed by univariate analysis of the top five metabolic pathways. Based on the analysis of soil and metabolomics, it was found that soil water content was also a factor affecting E. saxatilis metabolism. According to the difference of vertical height gradient, ephedrine and pseudephedrine showed the same change in vertical altitude under different mountains. Ephedrine increased as the altitude gradient increased, and pseudoephedrine decreased as the altitude gradient decreased. Our results provide valuable information for further study of metabolic mechanism and efficacy stability. It provides useful reference for the research of E. saxatilis planting in special area.
Assuntos
Ephedra , Efedrina , Tibet , Pseudoefedrina , Altitude , China , Preparações de Plantas , SoloRESUMO
The market for illicit drugs and new psychoactive substances (NPS) has grown significantly and people attending festivals have been identified as being at high risk (high extent and frequency of substance use). Traditional public health surveillance data sources have limitations (high costs, long implementation times, and ethical issues) and wastewater-based epidemiology (WBE) can cost-effectively support surveillance efforts. Influent wastewater samples were analyzed for NPS and illicit drug consumption collected during New Year period (from 29-Dec-2021 to 4-Jan-2022) and a summer Festival (from 29-June-2022 to 12-July-2022) in a large city in Spain. Samples were analyzed for phenethylamines, cathinones, opioids, benzodiazepines, plant-based NPS, dissociatives, and the illicit drugs methamphetamine, MDA, MDMA, ketamine, heroin, cocaine, and pseudoephedrine by liquid chromatography mass spectrometry. High consumption rates of specific NPS and established illicit drugs were identified at the peak of each event. Furthermore, a dynamic change in NPS use (presence and absence of substances) was detected over a period of six months. Eleven NPS, including synthetic cathinones, benzodiazepines, plant-based NPS and dissociatives, and seven illicit drugs were found across both the New Year and summer Festival. Statistically significant differences (p < 0.05) were seen for 3-MMC (New Year vs summer Festival), eutylone (New Year vs summer Festival), cocaine (summer Festival vs normal week and summer Festival vs New Year), MDMA (New Year vs normal week and summer Festival vs normal week), heroin (summer Festival vs New Year) and pseudoephedrine (summer Festival vs New Year). This WBE study assessed the prevalence of NPS and illicit drugs at festivals following the reduction of the COVID-19 pandemic restrictions highlighting the high use of specific substances at the peak of each event. This approach identified in a cost-effective and timely manner without any ethical issues the most used drugs and changes in use patterns and, thus, can complement public health information.
Assuntos
COVID-19 , Cocaína , Drogas Ilícitas , N-Metil-3,4-Metilenodioxianfetamina , Transtornos Relacionados ao Uso de Substâncias , Humanos , Férias e Feriados , Prevalência , Heroína , Pandemias , Pseudoefedrina , COVID-19/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , PsicotrópicosRESUMO
A previous 1H-NMR method allowed the quantification of ephedrine alkaloids; however, there were some disadvantages. The cyclized derivatives resulted from the impurities of diethyl ether were identified and benzene was selected as the better extraction solvent. The locations of ephedrine alkaloids were confirmed with 2D NMR. Therefore, a specific 1H-NMR method has been modified for the quantification of ephedrine alkaloids. Accordingly, twenty Ephedrae Herba samples could be classified into three classes: (I) E. sinica-like species; (II) E. intermedia-like species; (III) others (lower alkaloid contents). The results indicated that ephedrine and pseudoephedrine are the major alkaloids in Ephedra plants, but the concentrations vary greatly determined by the plant species and the collection locations.
Assuntos
Alcaloides , Ephedra , Efedrina , Espectroscopia de Prótons por Ressonância Magnética , Pseudoefedrina , Efedrina/análise , Pseudoefedrina/análise , Ephedra/química , Alcaloides/análise , Espectroscopia de Prótons por Ressonância Magnética/métodosRESUMO
We describe a man in his 40s with a history of chronic intranasal cocaine use and C5-C7 incomplete quadriplegia complicated by neurogenic orthostatic hypotension, admitted to the intensive care unit for worsening bradycardia and hypotension requiring initiation of dopamine and an increase of his home midodrine dose. The patient experienced refractory bradycardia and hypotension with weaning of dopamine, and therefore a recommendation was made to add pseudoephedrine to his current regimen. This case describes the addition of pseudoephedrine to facilitate weaning off intravenous vasopressors within 24 hours in a patient with refractory bradycardia and hypotension secondary to autonomic dysfunction.
Assuntos
Doenças do Sistema Nervoso Autônomo , Hipotensão Ortostática , Hipotensão , Midodrina , Masculino , Humanos , Pseudoefedrina/efeitos adversos , Bradicardia/induzido quimicamente , Bradicardia/tratamento farmacológico , Dopamina/uso terapêutico , Hipotensão/induzido quimicamente , Hipotensão/tratamento farmacológico , Hipotensão/complicações , Doenças do Sistema Nervoso Autônomo/complicações , Doenças do Sistema Nervoso Autônomo/tratamento farmacológico , Hipotensão Ortostática/etiologia , Midodrina/efeitos adversosRESUMO
Ephedra sinica Stapf. is a shrubby plant widely used in traditional Chinese medicine due to its high level of medicinal value, thus, it is in high demand. Ephedrine (E) and pseudoephedrine (PE) are key medicinal components and quality indicators for E. sinica. These two ephedrine-type alkaloids are basic elements that exert the medicinal effect of E. sinica. Recently, indiscriminate destruction and grassland desertification have caused the quantity and quality of these pharmacological plants to degenerate. Predicting potentially suitable habitat for high-quality E. sinica is essential for its future conservation and domestication. In this study, MaxEnt software was utilized to map suitable habitats for E. sinica in Inner Mongolia based on occurrence data and a set of variables related to climate, soil, topography and human impact. The model parametrization was optimized by evaluating alternative combinations of feature classes and values of the regularization multiplier. Second, a geospatial quality model was fitted to relate E and PE contents to the same environmental variables and to predict their spatial patterns across the study area. Outputs from the two models were finally coupled to map areas predicted to have both suitable conditions for E. sinica and high alkaloid content. Our results indicate that E. sinica with high-quality E content was mainly distributed in the Horqin, Ulan Butong and Wulanchabu grasslands. E. sinica with high-quality PE content was primarily found in the Ordos, Wulanchabu and Ulan Butong grasslands. This study provides scientific information for the protection and sustainable utilization of E. sinica. It can also help to control and prevent desertification in Inner Mongolia.
Assuntos
Alcaloides , Medicamentos de Ervas Chinesas , Ephedra sinica , Ephedra , Humanos , Efedrina , Medicamentos de Ervas Chinesas/análise , China , PseudoefedrinaRESUMO
BACKGROUND: Seizures are common neurological emergencies in the elderly that are frequently provoked. Geriatrics have higher rates of neurological disorders and other comorbidities that could affect seizure threshold. CASE PRESENTATION: An 83-year-old male Arabic patient presented to the emergency department with an acute confusional state and urinary incontinence followed by a witnessed tonic-clonic seizure in the hospital. Thorough investigations and imaging were positive only for nonspecific magnetic resonant imaging findings with a negative electroencephalogram. The patient was diagnosed with provoked seizure due to over-the-counter cold medications that included pseudoephedrine and caffeine. He was not prescribed antiepileptic medications at discharge and did not develop subsequent seizures up to this date. CONCLUSION: Over-the-counter cough and cold medications with sympathomimetic ingredients can be associated with provoked seizures in the elderly. Physicians should be aware of the potentially serious adverse events associated with commonly used nonprescription sympathomimetics such as pseudoephedrine and caffeine in elderly patients.