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2.
Int J Mol Sci ; 22(13)2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34281274

RESUMO

It has been recognized that serotonin 2A receptor (5-HT2A) agonist 2,5-dimethoxy-4-iodo-amphetamine (DOI) impairs serotonergic homeostasis. However, the mechanism of DOI-induced serotonergic behaviors remains to be explored. Moreover, little is known about therapeutic interventions against serotonin syndrome, although evidence suggests that ginseng might possess modulating effects on the serotonin system. As ginsenoside Re (GRe) is well-known as a novel antioxidant in the nervous system, we investigated whether GRe modulates 5-HT2A receptor agonist DOI-induced serotonin impairments. We proposed that protein kinase Cδ (PKCδ) mediates serotonergic impairments. Treatment with GRe or 5-HT2A receptor antagonist MDL11939 significantly attenuated DOI-induced serotonergic behaviors (i.e., overall serotonergic syndrome behaviors, head twitch response, hyperthermia) by inhibiting mitochondrial translocation of PKCδ, reducing mitochondrial glutathione peroxidase activity, mitochondrial dysfunction, and mitochondrial oxidative stress in wild-type mice. These attenuations were in line with those observed upon PKCδ inhibition (i.e., pharmacologic inhibitor rottlerin or PKCδ knockout mice). Furthermore, GRe was not further implicated in attenuation mediated by PKCδ knockout in mice. Our results suggest that PKCδ is a therapeutic target for GRe against serotonergic behaviors induced by DOI.


Assuntos
Ginsenosídeos/farmacologia , Proteína Quinase C-delta/metabolismo , Antagonistas da Serotonina/farmacologia , Síndrome da Serotonina/prevenção & controle , Acetofenonas/farmacologia , Anfetaminas/toxicidade , Animais , Comportamento Animal/efeitos dos fármacos , Comportamento Animal/fisiologia , Benzopiranos/farmacologia , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Piperidinas/farmacologia , Proteína Quinase C-delta/deficiência , Proteína Quinase C-delta/genética , Inibidores de Proteínas Quinases/farmacologia , Serotonina/fisiologia , Agonistas do Receptor de Serotonina/farmacologia , Síndrome da Serotonina/induzido quimicamente , Síndrome da Serotonina/fisiopatologia
3.
J Sports Sci Med ; 20(2): 328-338, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34211326

RESUMO

Sports nutrition supplements have previously been reported to contain undeclared doping substances. The use of such supplements can lead to general health risks and may give rise to unintentional doping violations in elite sports. To assess the prevalence of doping substances in a range of high-risk sports nutrition supplements available from Dutch web shops. A total of 66 sports nutrition supplements - identified as potentially high-risk products claiming to modulate hormone regulation, stimulate muscle mass gain, increase fat loss, and/or boost energy - were selected from 21 different brands and purchased from 17 web shops. All products were analyzed for doping substances by the UK life sciences testing company LGC, formerly known as the Laboratory of the Government Chemist, using an extended version of their ISO17025 accredited nutritional supplement screen. A total of 25 out of the 66 products (38%) contained undeclared doping substances, which included high levels of the stimulants oxilofrine, ß-methylphenethylamine (BMPEA) and N,ß-dimethylphenethylamine (NBDMPEA), the stimulant 4-methylhexan-2-amine (methylhexaneamine, 1,3-dimethylamylamine, DMAA), the anabolic steroids boldione (1,4-androstadiene-3,17-dione) and 5-androstene-3ß,17α-diol (17α-AED), the beta-2 agonist higenamine and the beta-blocker bisoprolol. Based upon the recommended dose and the potential variability of analyte concentration, the ingestion of some products identified within this study could pose a significant risk of unintentional doping violations. In addition to inadvertent doping risks, the prescribed use of 3 products (4.5%) could likely impose general health risks.


Assuntos
Suplementos Nutricionais/análise , Doping nos Esportes , Contaminação de Medicamentos , Agonistas Adrenérgicos beta/análise , Antagonistas Adrenérgicos beta/análise , Alcaloides/análise , Anfetaminas/análise , Androstadienos/análise , Humanos , Prevalência , Medição de Risco , Congêneres da Testosterona/análise , Tetra-Hidroisoquinolinas/análise
4.
Molecules ; 26(13)2021 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-34206603

RESUMO

The vaporization enthalpy, and vapor pressure as a function of temperature of N-ethylamphetamine, a substance used in the 1950s as an appetite suppressant and more currently abused as a designer drug, is reported. Its physical properties are compared to those of S (+)-N-methamphetamine, a substance whose physiological properties it mimics. A vaporization enthalpy of (62.4 ± 4.4) kJ·mol-1 and vapor pressure of (19 ± 11) Pa at T = 298.15 K has been evaluated by correlation gas chromatography. Results are compared to estimated values and to the limited amount of experimental property data available.


Assuntos
Anfetaminas/química , Modelos Químicos , Termodinâmica , Pressão de Vapor , Cromatografia Gasosa , Volatilização
5.
Talanta ; 233: 122597, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34215085

RESUMO

1-(3-chlorophenyl) piperazine (mCPP) is a synthetic drug with hallucinogenic effects that has often been found in seized samples. In this context, easy to use point-of-care tests can be of great value in preliminary forensic analysis. Herein, we proposed a simple, fast, and portable electrochemical method for the detection of mCPP in seized samples. The method is based on the use of disposable screen-printed carbon electrodes (SPCE) and rapid screening procedures by square-wave voltammetry using minimal sample sizes (100 µL). mCPP showed an irreversible electrochemical oxidation process at +0.65 V on SPCE (vs Ag) using 0.04 mol L-1 Britton Robinson (BR) buffer solution (pH 7) as the supporting electrolyte. The proposed method exhibited a linear correlation (r = 0.998) between peak current and mCPP concentration in the range of 1-30 µmol L-1 (LOD = 0.1 µmol L-1). Interference studies were performed for adulterants and other classes of drugs of abuse, which can also be found in seized samples containing mCPP, such as caffeine, amphetamine, methamphetamine, 1-benzylpiperazine, 3,4-methylenedioxymethamphetamine, methylone, mephedrone, ethylone and 3, 4-methylenedioxypyrovalerone. The developed method presents great potential as a rapid and simple screening tool to detect mCPP in forensic samples.


Assuntos
N-Metil-3,4-Metilenodioxianfetamina , Anfetaminas , Eletrodos , Piperazinas
6.
Se Pu ; 39(3): 271-280, 2021 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-34227308

RESUMO

Enantiomers are ubiquitous in nature, and they are especially important in the field of pharmaceutical chemistry. Although the enantiomers of chiral drugs have identical chemical structures, they differ notably in their pharmacological, toxicological, pharmacokinetic, metabolic, and other biological activities. The same is true for amphetamines, ketamine, and cathinones, as the chiral separation of these three drugs is representative of drugs. Gas chromatography (GC), high performance liquid chromatography (HPLC), and capillary electrophoresis (CE) are widely used for the chiral separation of these three kinds of drugs. There are some similarities among the three methods for the chiral separation of amphetamines, ketamine, and cathinones: n-trifluoroacetyl-L-prolinyl chloride and (+)R-α-methoxy-α-trifluoromethylphenylacetic acid are the two typical chiral derivatization reagents used in GC. In HPLC, three kinds of chiral stationary phases are used: proteins, polysaccharides, and macrocyclic antibiotics. Cyclodextrin and its derivatives are most commonly used in CE. However, these three methods have inherent shortcomings. In the case of GC, impurities produced during chiral derivatization may interfere with the analysis, and high reaction temperatures affect the efficiency of chiral separation. HPLC has limited application scope and is expensive. In CE, there has no established process to determine the appropriate chiral selector. In recent years, research into application of the chiral separation of the above-mentioned three kinds of drugs has its own characteristics in forensic toxicology. The chiral separation of amphetamine drugs is mostly used to infer the prototype and synthesis route of drugs on the market. The chiral separation of ketamine involves a variety of biological samples. For cathinones, chiral separation methods emphasize their wide applicability. In this review, 66 reports published in professional local and overseas magazines during the past decade are collated. The characteristics of the enantiomers of amphetamines, ketamine, and cathinones as well as the mechanism of chiral recognition are briefly introduced. The commonness of the research and the application of chiral separation in forensic toxicology are reviewed. This paper proposes that the chiral separation of drugs can be further investigated from the following three aspects: 1) the use of computer technology to establish a molecular model for exploring the mechanism of chiral recognition; 2) developing new technologies for chiral separation and carrying out commercial research on the supercritical fluid method; 3) applying chiral separation to judicial practice, pharmaceutical research and development, and other practical fields.


Assuntos
Alcaloides , Anfetaminas/isolamento & purificação , Ketamina , Alcaloides/isolamento & purificação , Cromatografia Gasosa , Cromatografia Líquida de Alta Pressão , Eletroforese Capilar , Ketamina/isolamento & purificação , Estereoisomerismo
7.
Eur J Pharmacol ; 901: 174070, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-33798598

RESUMO

The aim of this study was to investigate the reaction of pancreatic and mesenteric artery to 5-hydroxytryptamine (5-HT, serotonin) and the mechanism of nitric oxide in diabetes. Diabetic mice were induced by streptozotocin through intraperitoneal injection. The vascular tension of the pancreatic, mesenteric and brain basilar arteries in diabetic and control mice were measured by myograph in the applications of angiotensin II, 5-HT, 5-HT2A receptor agonist 2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI), 5-HT1B/1D receptor agonist sumatriptan, 5-HT2B receptor agonist BW723C86, 5-HT1D receptor antagonist Palonosetron and 5-HT2 receptor antagonist Sarpogrelate. The effect of 5-HT on arteries pretreated with L-NAME and sodium nitroprusside (SNP) on arteries pretreated with norepinephrine were measured. The mRNA expressions of eNOS, 5-HT1B, 5-HT1D, 5-HT2A and 5-HT2B in pancreatic and mesenteric arteries were measured by Real-time PCR. The concentration of 5-HT in plasma and eNOS in pancreatic and mesenteric arteries were tested. Our results showed that the tension of pancreatic and mesenteric arteries in diabetic mice impaired to 5-HT, but not Ang II, and to DOI and sumatriptan, but normalized by incubation with L-NAME. Pancreatic and mesenteric arteries showed no differences to SNP after pretreated with NE between diabetic and control mice. The mRNA of eNOS and 5-HT receptors in pancreatic and mesenteric artery showed no difference between control and diabetic mice. We conclude that the effect of 5-HT on the tension of pancreatic and mesenteric arteries decrease in diabetic mice. It may due to the decreased activity of 5-HT receptors and the activation of eNOS, which causes nitric oxide to release more and makes the tension of vessels decreased.


Assuntos
Diabetes Mellitus Experimental/fisiopatologia , Artérias Mesentéricas/fisiopatologia , Pâncreas/fisiopatologia , Serotonina/fisiologia , Anfetaminas/farmacologia , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , NG-Nitroarginina Metil Éster/farmacologia , Doadores de Óxido Nítrico/farmacologia , Óxido Nítrico Sintase Tipo III/antagonistas & inibidores , Norepinefrina , Receptor 5-HT2A de Serotonina/efeitos dos fármacos , Agonistas do Receptor 5-HT1 de Serotonina/farmacologia , Agonistas do Receptor 5-HT2 de Serotonina/farmacologia
8.
Clin Biochem ; 93: 112-118, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33882283

RESUMO

INTRODUCTION: The aim of this study was to evaluate the analytical performance of the Kite Biotechnology Oral fluid (OF) screening test device, which is used for roadside screening of cannabis, opiates, amphetamines, methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA), cocaine and benzodiazepines by comparing samples with matched plasma samples, analysed via liquid chromatography-tandem mass spectrometry (LC-MS/MS) for confirmation. METHODS: OF and plasma samples were obtained simultaneously from a total of 100 subjects. OF samples were analysed by OF screening test based on immunochromatography. The OF screening test cut-off values were 50 ng/mL for amphetamines (d-amphetamine) and methamphetamine/MDMA (d-methamphetamine), 30 ng/mL for cocaine (benzoylecgonine), 40 ng/mL for opiates (morphine), 20 ng/mL for benzodiazepines (nordazepam), and 25 ng/mL for cannabis (Δ9-tetrahydrocannabinol). LC-MS/MS method validation was performed according to the CLSI C62-A recommendations with the following parameters: matrix effect, lower limit of quantification (LLOQ), linearity, intra-day and inter-day precision and accuracy. RESULTS: The overall specificity, accuracy and negative predictive values (NPV) were acceptable and met the DRUID standard of >80%. The OF screening test device showed good sensitivity for cocaine, amphetamines and opiates, whereas it indicated poor sensitivity for methamphetamine/MDMA (66.7%) and failed to detect cannabis and benzodiazepines. CONCLUSION: The present study is the first report to evaluate the Kite Biotechnology OF screening test device. The diagnostic performance of the OF screening test device was acceptable for opiates, cocaine and amphetamines, but it was insufficient for methamphetamine/MDMA, benzodiazepines and cannabis because of sensitivity issues.


Assuntos
Imunoensaio/instrumentação , Imunoensaio/métodos , Saliva/química , Detecção do Abuso de Substâncias/instrumentação , Detecção do Abuso de Substâncias/métodos , Anfetaminas/análise , Cocaína/análogos & derivados , Cocaína/análise , Confiabilidade dos Dados , Dirigir sob a Influência , Dronabinol/análise , Análise de Falha de Equipamento , Feminino , Toxicologia Forense/instrumentação , Toxicologia Forense/métodos , Humanos , Drogas Ilícitas/análise , Masculino , Metanfetamina/análise , Morfina/análise , Nordazepam/análise , Plasma/química , Valor Preditivo dos Testes , Espectrometria de Massas em Tandem
9.
Clin Toxicol (Phila) ; 59(11): 975-981, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33755516

RESUMO

BACKGROUND: Weight loss and sports supplements containing deterenol have been associated with serious adverse events including cardiac arrest. OBJECTIVE: To determine the presence and quantity of experimental stimulants in dietary supplements labeled as containing deterenol sold in the United States. METHODS: Dietary supplements available for sale in the US and labeled as containing deterenol or one of its synonyms (e.g., isopropylnorsynephrine and isopropyloctopamine) were purchased online. For each brand, one container or subsample was analyzed by NSF International (Ann Arbor, MI) and one container or subsample by the Netherland's National Institute for Public Health and the Environment (RIVM, Bilthoven, The Netherlands). When differences existed between the two containers or subsamples of the same brand, both products were reanalyzed by Sciensano (Brussels, Belgium). NSF International carried out qualitative and quantitative analyses using ultra-high-performance liquid chromatography (UHPLC) quadrupole-Orbitrap mass spectrometry. RIVM performed qualitative and quantitative analysis using UHPLC quadrupole time-of-flight mass spectrometry. Sciensano carried out qualitative analysis using UHPLC quadrupole-Orbitrap mass spectrometry. RESULTS: Seventeen brands of supplements were analyzed. Many brands included more than one prohibited stimulant in the same product: 4 brands (24%, 4/17) included 2 stimulants, 2 (12%, 2/17) combined 3 stimulants, and 2 (12%, 2/17) combined 4 stimulants. The range of quantities per recommended serving size of the 9 stimulants detected were 2.7 mg to 17 mg of deterenol; 1.3 mg to 20 mg of phenpromethamine (Vonedrine); 5.7 mg to 92 mg of beta-methylphenylethylamine (BMPEA); 18 mg to 73 mg of octodrine; 18 mg to 55 mg of oxilofrine; 48 mg of higenamine; 17 mg of 1,3-dimethylamylamine (1,3-DMAA); 1.8 mg to 6.6 mg of 1,3-dimethylbutylamine (1,3-DMBA); and 5.3 mg of 1,4-dimethylamylamine (1,4-DMAA). CONCLUSION: Weight loss and sports supplements listing deterenol as an ingredient contained 9 prohibited stimulants and 8 different mixtures of stimulants, with as many as 4 experimental stimulants per product. These cocktails of stimulants have never been tested in humans and their safety is unknown.


Assuntos
Agonistas Adrenérgicos/análise , Fármacos Antiobesidade/análise , Estimulantes do Sistema Nervoso Central/análise , Suplementos Nutricionais/análise , Agonistas Adrenérgicos/efeitos adversos , Alcaloides/análise , Aminas/análise , Anfetaminas/análise , Fármacos Antiobesidade/efeitos adversos , Estimulantes do Sistema Nervoso Central/efeitos adversos , Qualidade de Produtos para o Consumidor , Suplementos Nutricionais/efeitos adversos , Efedrina/análogos & derivados , Efedrina/análise , Heptanos/análise , Humanos , Octopamina/análogos & derivados , Octopamina/análise , Medição de Risco , Tetra-Hidroisoquinolinas/análise , Estados Unidos
10.
Bioanalysis ; 13(6): 493-511, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33719527

RESUMO

This article covers current methods and applications in chiral analysis from 2010 to 2020 for biosamples in clinical research and forensic toxicology. Sample preparation for aqueous and solid biological samples prior to instrumental analysis were discussed in the article. GC, HPLC, capillary electrophoresis and sub/supercritical fluid chromatography provide the efficient tools for chiral drug analysis coupled to fluorescence, UV and MS detectors. The application of chiral analysis is discussed in the article, which involves differentiation between clinical use and drug abuse, pharmacokinetic studies, pharmacology/toxicology evaluations and chiral inversion. Typical chiral analytes, including amphetamines and their analogs, anesthetics, psychotropic drugs, ß-blockers and some other chiral compounds, are also reviewed.


Assuntos
Anfetaminas/análise , Anfetaminas/toxicidade , Toxicologia Forense , Cromatografia com Fluido Supercrítico , Eletroforese Capilar , Humanos , Espectrometria de Massas
11.
J Clin Psychopharmacol ; 41(3): 310-314, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33657069

RESUMO

PURPOSE/BACKGROUND: This study aimed to evaluate the frequency of needing to switch the initial treatment of a stimulant to the alternative family in newly referred, medication-naive adults with attention-deficit/hyperactivity disorder (ADHD) initiating treatment with stimulants. METHODS/PROCEDURES: Subjects were 49 unmedicated adults (18-45 years old) with Diagnostic and Statistical Manual of Disorders (Fifth Edition) ADHD who initiated treatment with a stimulant. Before the clinical assessment with an expert clinician, participants completed the Adult Self-Report, Behavior Rating Inventory of Executive Function-Adult Version, Emotional Dysregulation Subscale of the Barkley Current Behavior Scale-Self-report, and Mind Wandering Questionnaire. The rate of switching was examined using information from the electronic medical record for up to three clinical follow-up visits. Comparisons were made between those who did and did not need to switch on baseline demographic and clinical characteristics. FINDINGS/RESULTS: Sixty-seven percent of ADHD patients were initially prescribed a methylphenidate product, and 33%, an amphetamine product. Forty-one percent of ADHD patients needed to switch from their initially prescribed stimulant family within 90 days of initiating treatment because of poor tolerability. Whereas the rate of switching was significantly higher in those initially prescribed methylphenidate, the rate of patients who required changes in formulation (long- to short-acting and vice versa) or additional antianxiety or antidepressant treatment ("strugglers") was higher in those taking amphetamine. Switchers were more impaired on the Adult Self-Report Intrusive scale, whereas nonswitchers were more impaired on the Behavior Rating Inventory of Executive Function Inhibit and Task Monitor scales. However, these findings were small and of unclear clinical significance. IMPLICATIONS/CONCLUSIONS: Forty-one percent of medication-naive adults with ADHD initiating stimulant treatment required a switch from the initially prescribed stimulant family to the alternative one because of poor tolerability. Switching could not be adequately predicted by baseline demographic or clinical characteristics. These findings call for improved efforts to help identify predictors of response to stimulant treatment in adults with ADHD to avoid unnecessary delays in identifying a safe and effective treatment for these patients.


Assuntos
Anfetaminas/administração & dosagem , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Estimulantes do Sistema Nervoso Central/administração & dosagem , Metilfenidato/administração & dosagem , Adolescente , Adulto , Anfetaminas/efeitos adversos , Estimulantes do Sistema Nervoso Central/efeitos adversos , Substituição de Medicamentos/estatística & dados numéricos , Registros Eletrônicos de Saúde , Função Executiva , Feminino , Seguimentos , Humanos , Masculino , Metilfenidato/efeitos adversos , Pessoa de Meia-Idade , Projetos Piloto , Escalas de Graduação Psiquiátrica , Resultado do Tratamento , Adulto Jovem
12.
Neurosci Biobehav Rev ; 125: 208-220, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33639179

RESUMO

This systematic review and meta-analysis assess the change in inflammation biomarkers level among chronic psychoactive substance users. To meet the required inclusion criteria, all studies had to describe human participants with an age ≥18y., experiencing chronic psychostimulant (nicotine, amphetamine, cocaine), sedative (benzodiazepine, opioids) and/or cannabinoid use. The comparison group was defined as healthy participants. Studies where included if they reported at least one of the pro/inflammatory biomarkers. Study bias was examined by Funnel plots and heterogeneity by computing the I2 statistics. Only 21 eligible studies were selected based on 26,216 study participants. A small and significant effect size of 0.18 mg/l (95 % CI:0.10-0.27) was detected in favour of chronic smokers (z = 4.33;P < 0.0001). There was evidence of publication bias for studies measuring IL-6 and IL-10 association with cocaine and IL-6 in association with cannabis. In summary, except for chronic tobacco users, there was no evidence of association between other chronic substances abuse and inflammatory levels. More studies are needed to inform policy and decision makers about the utility of anti-inflammatory based targeted intervention programmes.


Assuntos
Cannabis , Cocaína , Anfetaminas , Analgésicos Opioides , Humanos , Inflamação
13.
Int J Legal Med ; 135(2): 465-471, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33392654

RESUMO

Hair is a preferred material to detect exposure or use of illegal drugs in children. In the present study, we investigated a total of 387 hair samples for commonly applied illegal drugs of children up to 16 years. Analysis was by liquid chromatography/mass spectrometry with LOQs of 0.01 ng/mg hair for all analytes except tetrahydrocannabinol carboxylic acid with an LOQ of 0.1 pg/mg hair. Results were firstly compared with our in-house statics on results from adults' hair, and secondly to literature data. We started from the assumption that drug concentrations decrease with increasing age.Results were assigned to 4 different age groups (< 1 year, 1-< 6 years, 6-< 14 years, 14-16 years). As expected, higher results were obtained in age groups 1 and 2. The lowest concentrations were present in age group 3, whereas an increase could be observed in group 4 except heroin. In babies, positive results may be due to in utero exposure, breast milk feeding, and a close physical contact. All drugs under investigation such as cannabinoids, cocaine, amphetamines, and opiates have been detected in breast milk as well as in skin excretions such as sebum, sweat and cutaneous cells. For most drugs, average concentrations in children hair were lower than in adult hair when compared with our in-house statistics. Interestingly, the increase of cannabinoids, cocaine, and amphetamines concentrations in adolescents' hair points to a deliberate use of these drugs possibly in addition to passive exposure. This observation shows that age groups 1 and 4 are most vulnerable if caregivers or parents are drug users, even if the sources of positive drug findings differ.


Assuntos
Análise do Cabelo , Cabelo/química , Drogas Ilícitas/análise , Menores de Idade , Detecção do Abuso de Substâncias/métodos , Adolescente , Fatores Etários , Anfetaminas/análise , Canabinoides/análise , Criança , Pré-Escolar , Cromatografia Líquida , Cocaína/análise , Feminino , Heroína/análise , Humanos , Lactente , Masculino , Espectrometria de Massas em Tandem
14.
Am J Forensic Med Pathol ; 42(1): 57-61, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-32773434

RESUMO

ABSTRACT: Synthetic cathinones are one of the major pharmacological families of new psychoactive substances and 4-methylethcathinone (4-MEC) has emerged in recent years as a recreational psychostimulant. We report a case of a 35-year-old man found dead and naked at home by his friend. Although no anatomic cause of death was observed at autopsy, toxicological analysis identified 4-MEC and hydroxyzine at therapeutic level (160 ng/mL). 4-Methylethcathinone was quantified in autopsy samples by a validated method consisting in liquid-liquid extraction and gas chromatography coupled to tandem mass spectrometry: peripheral blood, 14.6 µg/mL; cardiac blood, 43.4 µg/mL; urine, 619 µg/mL; vitreous humor, right 2.9 µg/mL and left 4.4 µg/mL; bile, 43.5 µg/mL; and gastric content, 28.2 µg/mL. The cause of death was 4-MEC intoxication and the manner of death could be either accidental or suicidal. The literature concerning 4-MEC was reviewed, focusing on distribution in classical postmortem matrices and 4-MEC metabolism and postmortem redistribution and stability.


Assuntos
Anfetaminas/envenenamento , Estimulantes do Sistema Nervoso Central/envenenamento , Propiofenonas/envenenamento , Adulto , Anfetaminas/análise , Bile/química , Estimulantes do Sistema Nervoso Central/análise , Overdose de Drogas , Cromatografia Gasosa-Espectrometria de Massas , Conteúdo Gastrointestinal/química , Humanos , Masculino , Propiofenonas/análise , Abuso de Substâncias por Via Intravenosa/complicações , Corpo Vítreo/química
15.
Curr Opin Rheumatol ; 33(1): 24-33, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33186242

RESUMO

PURPOSE OF REVIEW: To review understand the epidemiology, background, neuropharmacology, and histopathology of literature verified cases, and likely etiopathogenic mechanisms. RECENT FINDINGS: There are only a handful of histologically confirmed patients in the literature with cerebral vasculitis because of drug abuse. SUMMARY: There is little justification for invasive laboratory investigation given the ready availability of highly accurate vascular neuroimaging techniques to dictate management, which usually rests upon avoidance of further exposure and minimizing the secondary neurotoxic effects of the abused substances and polypharmacy use.


Assuntos
Drogas Ilícitas/efeitos adversos , Transtornos Relacionados ao Uso de Substâncias/complicações , Vasculite do Sistema Nervoso Central/induzido quimicamente , Adulto , Anfetaminas/efeitos adversos , Analgésicos Opioides/efeitos adversos , Estimulantes do Sistema Nervoso Central/efeitos adversos , Cocaína/efeitos adversos , Feminino , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Neuroimagem/métodos , Polimedicação , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Vasculite do Sistema Nervoso Central/diagnóstico por imagem , Vasculite do Sistema Nervoso Central/epidemiologia
16.
J Anal Toxicol ; 45(9): 985-992, 2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-33031519

RESUMO

Over the last two decades, misuse of 4-fluoroamphetamine (4-FA) became an emerging issue in many European countries. Stimulating effects last for 4-6 hours and can impact psychomotor performance. The metabolism of amphetamine-type stimulants is stereoselective and quantification of (R)- and (S)-enantiomers has been suggested for assessing time of use. To date, no data on enantioselective pharmacokinetics is available for 4-FA in serum samples. An enantioselective liquid chromatography-tandem mass spectrometry (LC-MS-MS) method was developed using a chiral Phenomenex® Lux 3 µm AMP column. Validation of the method showed satisfactory selectivity, sensitivity, linearity (0.5-250 ng/mL), precision and accuracy. Recreational stimulant users orally ingested two doses (100 mg, n = 12; 150 mg, n = 5) of 4-FA. Blood samples were drawn prior to application and over a period of 12 hours after ingestion and analyzed for 4-FA enantiomers. Peak concentrations and corresponding times did not differ significantly between the enantiomers (mean (R)/(S)-ratio at tmax 1.05, 0.85-1.16). With mean 12.9 (8.3-16.1) hours, apparent elimination half-lives (t1/2) were significantly (P < 0.01) longer for (R)-4-FA than for (S)-4-FA (6.0 hours; range 4.4-10.2 hours) and independent of the dose given. Over time, (R)/(S)-concentration-ratios were linearly increasing in all subjects to maximum ratios of 2.00 (1.08-2.77) in the last samples (after 12 hours). The slopes of the (R)/(S)-ratio exhibited marked interindividual differences (0.023-0.157 h-1, mean 0.095 h-1). Ratios higher than 1.60 only appeared earliest after a minimum of 6 hours and therefore suggest the absence of acute drug effects. Different elimination half-lives of enantiomers lead to constantly increasing (R)/(S)-concentration-ratios. Consequently, ratios of 4-FA enantiomers in serum are a promising indicator for assessment of the time of drug consumption.


Assuntos
Anfetamina , Espectrometria de Massas em Tandem , Administração Oral , Anfetaminas , Cromatografia Líquida , Humanos , Estereoisomerismo
17.
J Am Pharm Assoc (2003) ; 61(1): e103-e109, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32912756

RESUMO

OBJECTIVES: Adderall (amphetamine-dextroamphetamine) is a controlled substance with harmful adverse effects if abused or misused. We assessed the availability of Adderall from common search engines, and evaluated the safety and marketing characteristics of online pharmacies selling Adderall. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: From December 2019 to February 2020, the phrase "buy Adderall online" was queried in four search engines: Google (N = 100), Bing (N = 100), Yahoo (N = 50) and DuckDuckGo (N = 50). Online pharmacies that claimed to sell Adderall and had unique Uniform Resource Locators, were active, free-access, and in English language were included. OUTCOME MEASURES: Online pharmacies were categorized as rogue, unclassified, or legitimate on the basis of LegitScript classifications. Safety and marketing characteristics, and costs were collected. RESULTS: Of the 62 online pharmacies found to sell Adderall, 61 were rogue or unclassified. Across all rogue and unclassified online pharmacies, prescriptions were not required (100%), pharmacist services were not offered (100%), and quantity limits were not placed on the number of Adderall purchases (100%). Rogue and unclassified online pharmacies appealed to cost, offering price discounts (61%), bulk discounts (67%), and coupon codes (70%). Contrary to their claims, cheaper prices were available for all formulations and dosages of Adderall from GoodRx than from these online pharmacies. Rogue and unclassified online pharmacies promoted and enabled the illicit purchase of Adderall, appealing to privacy (74%), offering purchase through cryptocurrency (74%), and claiming registration or accreditation of their sites (33%). CONCLUSION: Rogue online pharmacies are pervasive in search engine results, enabling the illicit purchase of Adderall without a prescription. Consumers are at risk of purchasing Adderall, a medication with high abuse potential, from unsafe sources. Law enforcement, regulatory agencies, and search engines should work to further protect consumers from unregistered and illegitimate online pharmacies selling Adderall.


Assuntos
Disponibilidade de Medicamentos Via Internet , Farmácias , Anfetaminas , Substâncias Controladas , Estudos Transversais , Humanos , Internet
18.
Int J STD AIDS ; 32(4): 304-313, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33308090

RESUMO

Female entertainment and sex workers (FESW) have high rates of alcohol and amphetamine-type stimulant (ATS) use, increasing risk for HIV/sexually transmitted infections (STI), and other negative outcomes. A prospective cohort of 1,198 FESW in a HIV/ATS use prevention intervention in Cambodia was assessed for alcohol and stimulant use disorders (AUD and SUD) using the Alcohol and Substance Use Involvement (ASSIST) scale. STI history was measured by self-report at baseline and at quarterly follow-up visits. Participants were asked if they had been diagnosed with an STI by a medical provider in the past 3 months. Marginal structural models were used to estimate joint effects of AUD and SUD on recent STI. At baseline, one-in-four screened AUD positive and 7% screened positive for SUD. At 18-months, 26% reported ≥1 recent STI. Accounting for time-varying and other known confounders, the adjusted odds ratio (AOR) for recent STI associated with AUD alone and SUD alone were 2.8 (95% CI:1.5-5.1) and 3.5 (95% CI:1.1-11.3), respectively. The AOR for joint effects of AUD and SUD was 5.7 (95% CI:2.2-15.2). AUD and SUD are independently and jointly associated with greater odds of STI among Cambodian FESW. Further research is critical for understanding how AUD and SUD potentiate biological and behavioural pathways that influence STI acquisition and to inform HIV risk-reduction interventions in FESW.


Assuntos
Transtornos Relacionados ao Uso de Álcool/complicações , Transtornos Relacionados ao Uso de Anfetaminas/complicações , Anfetaminas/administração & dosagem , Usuários de Drogas/psicologia , Profissionais do Sexo/estatística & dados numéricos , Doenças Sexualmente Transmissíveis/epidemiologia , Adulto , Transtornos Relacionados ao Uso de Álcool/epidemiologia , Transtornos Relacionados ao Uso de Anfetaminas/epidemiologia , Transtornos Relacionados ao Uso de Anfetaminas/psicologia , Camboja/epidemiologia , Feminino , Humanos , Estudos Prospectivos , Autorrelato , Profissionais do Sexo/psicologia , Sexo sem Proteção/psicologia , Sexo sem Proteção/estatística & dados numéricos
19.
Behav Brain Res ; 401: 113093, 2021 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-33359368

RESUMO

Psychedelic drugs acting as 5-hydroxyptryptamine 2A receptor (5-HT2AR) agonists have shown promise as viable treatments of psychiatric disorders, including obsessive-compulsive disorder. The marble burying test is a test of compulsive-like behavior in mice, and psychedelics acting as 5-HT2AR agonists can reduce digging in this test. We assessed the 5-HT2R contribution to the mechanisms of two 5-HT2A agonists on digging behavior in female NMRI mice, using citalopram as a reference compound. While the 5-HT2AR antagonist M100907 blocked the effect of DOI and the 5-HT2CR antagonist SB242084 blocked the effect of citalopram, neither antagonist blocked the effect of psilocybin. This study confirms 5-HT2AR agonism as a mechanism for reduced compulsive-like digging in the MB test and suggests that 5-HT2A and 5-HT2CRs can work in parallel on this type of behavior. Our results with psilocybin suggest that a 5-HT2R-independent mechanism also contributes to the effect of psilocybin on repetitive digging behavior.


Assuntos
Comportamento Compulsivo/tratamento farmacológico , Psilocibina/farmacologia , Receptor 5-HT2A de Serotonina/efeitos dos fármacos , Receptor 5-HT2C de Serotonina/efeitos dos fármacos , Agonistas do Receptor 5-HT2 de Serotonina/farmacologia , Antagonistas da Serotonina/farmacologia , Aminopiridinas/farmacologia , Anfetaminas/farmacologia , Animais , Comportamento Animal/efeitos dos fármacos , Citalopram/farmacologia , Modelos Animais de Doenças , Feminino , Fluorbenzenos/farmacologia , Indóis/farmacologia , Camundongos , Piperidinas/farmacologia , Psilocibina/administração & dosagem , Agonistas do Receptor 5-HT2 de Serotonina/administração & dosagem , Antagonistas da Serotonina/administração & dosagem , Inibidores de Captação de Serotonina/farmacologia
20.
Neuropharmacology ; 183: 107838, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31693871

RESUMO

5-Hydroxytryptamine 2A receptor (5-HT2AR) agonist psychedelics are increasingly recognized as potentially useful treatments of psychiatric disorders, such as obsessive-compulsive disorder, depression, anxiety, and drug dependence. There is limited understanding of the way they exert their therapeutic action, but inhibition of rigid behavior and cognition has been suggested as a key factor. To examine the role of 5-HT2ARs in modulating repetitive behavior, we tested two 5-HT2AR agonists, DOI, and the selective 25CN-NBOH, in two mouse tests of compulsive-like behavior. Using adult C57BL/6JOlaHsd male mice, we examined the effects of the two compounds on digging behavior in the marble burying test and on 8-OH-DPAT-disrupted spontaneous alternation behavior in the Y-maze. Both compounds dose-dependently decreased digging behavior in the marble burying test, indicating anti-compulsivity effects, which were not related to non-specific locomotor inhibition. Both 5-HT2AR agonists also reversed 8-OH-DPAT-reduced alternation ratio in the spontaneous alternation behavior test, although the effects were less pronounced than in the marble burying test. This suggests that the 5-HT2AR promotes exploratory behavior, but that the deficit produced by 8-OH-DPAT is too excessive to be fully reversed by 5-HT2AR agonists. This study shows that agonism of 5-HT2AR reduces repetitive behavioral patterns, supporting the theory that this is a potential new treatment approach to disorders of cognitive or behavioral inflexibility. This article is part of the special issue entitled 'Serotonin Research: Crossing Scales and Boundaries'.


Assuntos
8-Hidroxi-2-(di-n-propilamino)tetralina/farmacologia , Anfetaminas/farmacologia , Aprendizagem/efeitos dos fármacos , Transtorno Obsessivo-Compulsivo/tratamento farmacológico , Agonistas do Receptor 5-HT2 de Serotonina/farmacologia , Animais , Comportamento Animal/efeitos dos fármacos , Carbonato de Cálcio , Comportamento Exploratório/efeitos dos fármacos , Alucinógenos/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Atividade Motora/efeitos dos fármacos , Inibidores de Captação de Serotonina/farmacologia
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