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1.
Forensic Sci Int ; 360: 112062, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38781837

RESUMO

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 Químicos
2.
Chirality ; 36(5): e23676, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38736271

RESUMO

Among different substance classes, New Psychoactive Substances (NPS) comprise chiral amphetamines for stimulant and empathic effects. There is little knowledge in terms of clinical studies about possibly different effects of the two enantiomers of novel amphetamine derivatives. For this reason, there is a big demand for enantioseparation method development of this new substance class. Regarding gas chromatography, cyclodextrins proved to be effective for enantioseparation of NPS. In our attempt, an Astec® Chiraldex™ G-PN column containing 2,6-di-O-pentyl-3-propionyl-γ-cyclodextrin and a Lipodex™ D column containing heptakis-(2,6-di-O-pentyl-O-acetyl)-ß-cyclodextrin as chiral selector served as stationary phases in a Shimadzu GCMS-QP2010 SE system. Because of the special coating, maximum temperature is limited to 200 °C isothermal or 220 °C in programmed mode. To ensure detection, trifluoroacetic anhydride (TFAA) was used to increase sample volatility.1 As a result, 35 amphetamines were tested as their TFAA-derivatives. A screening method with a temperature gradient from 140 °C to 200 °C at a heating ramp of 1 °C per minute and final time of 5 min, showed baseline separation for seven and partial separations for 16 trifluoro acetylated amphetamines using the Chiraldex™ G-PN column. Six baseline and nine partial separations were observed with the Lipodex™ D column, respectively.


Assuntos
Anfetaminas , Estereoisomerismo , Anfetaminas/química , Anfetaminas/isolamento & purificação , Cromatografia Gasosa/métodos , Ciclodextrinas/química , Temperatura , Cromatografia Gasosa-Espectrometria de Massas/métodos
3.
Int J Mol Sci ; 25(7)2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38612632

RESUMO

Bile has emerged as an alternative matrix for toxicological investigation of drugs in suspected forensic cases of overdose in adults and intoxications in children. Toxicological investigation consists in screening and, subsequently, confirming the result with specific techniques, such as liquid chromatography with tandem mass spectrometry (LC-MS/MS). As there is no screening test on the market to test postmortem bile specimens, the novelty of this study was in investigating the applicability of a chemiluminescence immunoassay, designed for other matrices and available on the market, on bile and validate its use, testing the agreement with LC-MS/MS analysis. Bile specimens were obtained from 25 forensic cases of suspected death from overdose and intoxication. Sample preparation for bile screening consists simply in centrifugation and dilution. Confirmation analysis allows simultaneous identification of 108 drugs and was validated on bile. Kappa analysis assessed a perfect agreement (0.81-1) between the assays for benzodiazepines, methadone, opiates, cocaine, oxycodone, cannabinoids, buprenorphine and pregabalin; a substantial agreement (0.41-0.6) was reported for barbiturates. No agreement was assessed for amphetamines, due to an abundance of putrefactive amines in postmortem specimens. In conclusion, this fast and easy immunoassay could be used for initial screening of bile specimens, identifying presence of drugs, except amphetamines, with reliability.


Assuntos
Bile , Overdose de Drogas , Adulto , Criança , Humanos , Cromatografia Líquida , Luminescência , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem , Anfetaminas
4.
Neuropharmacology ; 252: 109949, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38636726

RESUMO

Psychedelic compounds have potentially rapid, long-lasting anxiolytic, antidepressive and anti-inflammatory effects. We investigated whether the psychedelic compound (R)-2,5-dimethoxy-4-iodoamphetamine [(R)-DOI], a selective 5-HT2A receptor partial agonist, decreases stress-related behavior in male mice exposed to repeated social aggression. Additionally, we explored the likelihood that these behavioral changes are related to anti-inflammatory properties of [(R)-DOI]. Animals were subjected to the Stress Alternatives Model (SAM), an escapable social stress paradigm in which animals develop reactive coping strategies - remaining in the SAM arena (Stay) with a social aggressor, or dynamically initiated stress coping strategies that involve utilizing the escape holes (Escape) to avoid aggression. Mice expressing these behavioral phenotypes display behaviors like those in other social aggression models that separate animals into stress-vulnerable (as for Stay) or stress-resilient (as for Escape) groups, which have been shown to have distinct inflammatory responses to social stress. These results show that Stay animals have heightened cytokine gene expression, and both Stay and Escape mice exhibit plasma and neural concentrations of the inflammatory cytokine tumor necrosis factor-α (TNFα) compared to unstressed control mice. Additionally, these results suggest that a single administration of (R)-DOI to Stay animals in low doses, can increase stress coping strategies such as increasing attention to the escape route, promoting escape behavior, and reducing freezing during socially aggressive interaction in the SAM. Lower single doses of (R)-DOI, in addition to shifting behavior to suggest anxiolytic effects, also concomitantly reduce plasma and limbic brain levels of the inflammatory cytokine TNFα.


Assuntos
Adaptação Psicológica , Agressão , Anfetaminas , Alucinógenos , Estresse Psicológico , Animais , Masculino , Estresse Psicológico/tratamento farmacológico , Estresse Psicológico/metabolismo , Alucinógenos/administração & dosagem , Alucinógenos/farmacologia , Adaptação Psicológica/efeitos dos fármacos , Adaptação Psicológica/fisiologia , Camundongos , Agressão/efeitos dos fármacos , Agressão/fisiologia , Anfetaminas/farmacologia , Anfetaminas/administração & dosagem , Camundongos Endogâmicos C57BL , Fator de Necrose Tumoral alfa/metabolismo , Agonistas do Receptor 5-HT2 de Serotonina/farmacologia , Agonistas do Receptor 5-HT2 de Serotonina/administração & dosagem , Reação de Fuga/efeitos dos fármacos , Capacidades de Enfrentamento
5.
Pharmacogenet Genomics ; 34(5): 149-153, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38517706

RESUMO

OBJECTIVES: Amphetamine-based medications are recommended as a first-line pharmacotherapy for the treatment of attention-deficit/hyperactivity disorder in children and adolescents. However, the efficacy and tolerability of these medications vary across individuals, which could be related to interindividual differences in amphetamine metabolism. This study examined if genotype-predicted phenotypes of the cytochrome P450 isozyme CYP2D6 were associated with self-reported side effects and symptom improvement in youth treated with amphetamines. METHODS: Two hundred fourteen participants aged 6-24 who had a history of past or current amphetamine treatment were enrolled from Western Canada. Amphetamine dose and duration information was collected from the participants along with questions regarding adherence, concomitant medications, symptom improvement and side effects. DNA was extracted from saliva samples and genotyped for CYP2D6 . Binomial logistic regression models were used to determine the effect of CYP2D6 metabolizer phenotype with and without correction for phenoconversion on self-reported symptom improvement and side effects. RESULTS: Genotype-predicted CYP2D6 poor metabolizers had significantly higher odds of reporting symptom improvement when compared to intermediate metabolizers (OR = 3.67, 95% CI = 1.15-11.7, P  = 0.029) after correction for phenoconversion and adjusting for sex, age, dose, duration, and adherence. There was no association between CYP2D6 metabolizer phenotype and self-reported side effects. CONCLUSION: Our findings indicate that phenoconverted and genotype-predicted CYP2D6 poor metabolizer phenotype is significantly associated with higher odds of symptom improvement in children and adolescents treated with amphetamine. If replicated, these results could inform the development of future dosing guidelines for amphetamine treatment in children and adolescents.


Assuntos
Anfetaminas , Transtorno do Deficit de Atenção com Hiperatividade , Citocromo P-450 CYP2D6 , Humanos , Citocromo P-450 CYP2D6/genética , Adolescente , Criança , Masculino , Feminino , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtorno do Deficit de Atenção com Hiperatividade/genética , Anfetaminas/efeitos adversos , Anfetaminas/administração & dosagem , Genótipo , Adulto Jovem , Variação Genética , Fenótipo , Estimulantes do Sistema Nervoso Central/efeitos adversos , Estimulantes do Sistema Nervoso Central/uso terapêutico , Estimulantes do Sistema Nervoso Central/administração & dosagem , Autorrelato
6.
Adv Pharmacol ; 99: 125-144, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38467479

RESUMO

Use of amphetamines during adolescence, a critical period of brain development and reorganization, may lead to particularly adverse outcomes that are long-lasting. Similarly, female users may be uniquely vulnerable to certain aspects of drug use. A recognition of the role of use during adolescence and sex on outcomes of amphetamine and methamphetamine exposure are of critical importance in understanding and treating substance use disorders. This chapter highlights what human research, which has been largely epidemiological, suggests about sex and age differences in drug use patterns and outcomes. We also discuss work in laboratory animals that has typically utilized rats or mice exposed to drugs in a non-contingent manner (i.e., involuntarily) or through volitional self-administration. Lastly, we draw attention to the fact that advancing our understanding of the effects of amphetamine and methamphetamine use, the development of problematic drug taking, and the mechanisms that contribute to relapse will require an emphasis on inclusion of age and sex as moderating factors in future studies.


Assuntos
Transtornos Relacionados ao Uso de Anfetaminas , Metanfetamina , Transtornos Relacionados ao Uso de Substâncias , Adolescente , Feminino , Humanos , Ratos , Camundongos , Animais , Anfetaminas/efeitos adversos , Metanfetamina/efeitos adversos , Anfetamina
7.
Adv Pharmacol ; 99: 83-124, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38467490

RESUMO

Synthetic cathinone derivatives comprise a family of psychoactive compounds structurally related to amphetamine. Over the last decade, clandestine chemists have synthesized a consistent stream of innovative cathinone derivatives to outpace governmental regulatory restrictions. Many of these unregulated substances are produced and distributed as designer drugs. Two of the principal chemical scaffolds exploited to expand the synthetic cathinone family are methcathinone and α-pyrrolidinopentiophenone (or α-pyrrolidinovalerophenone, α-PVP). These compounds' main physiological targets are monoamine transporters, where they promote addiction by potentiating dopaminergic neurotransmission. This chapter describes techniques used to study the pharmacodynamic properties of cathinones at monoamine transporters in vitro. Biochemical techniques described include uptake inhibition and release assays in rat brain synaptosomes and in mammalian expression systems. Electrophysiological techniques include current measurements using the voltage clamp technique. We describe a Ca2+ mobilization assay wherein voltage-gated Ca2+ channels function as reporters to study the action of synthetic cathinones at monoamine transporters. We discuss results from systematic structure-activity relationship studies on simple and complex cathinones at monoamine transporters with an emphasis on identifying structural moieties that modulate potency and selectivity at these transporters. Moreover, different profiles of selectivity at monoamine transporters directly predict compounds associated with behavioral and subjective effects within animals and humans. In conclusion, clarification of the structural aspects of compounds which modulate potency and selectivity at monoamine transporters is critical to identify and predict potential addictive drugs. This knowledge may allow prompt allocation of resources toward drugs that represent the greatest threats after drugs are identified by forensic laboratories.


Assuntos
Estimulantes do Sistema Nervoso Central , Catinona Sintética , Ratos , Animais , Humanos , Anfetaminas , Estimulantes do Sistema Nervoso Central/química , Estimulantes do Sistema Nervoso Central/farmacologia , Pirrolidinas/química , Pirrolidinas/metabolismo , Pirrolidinas/farmacologia , Mamíferos/metabolismo
8.
Fa Yi Xue Za Zhi ; 40(1): 37-42, 2024 Feb 25.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-38500459

RESUMO

OBJECTIVES: To investigate the toxicokinetic differences of 3,4-methylenedioxy-N-methylamphetamine (MDMA) and its metabolite 4,5-methylene dioxy amphetamine (MDA) in rats after single and continuous administration of MDMA, providing reference data for the forensic identification of MDMA. METHODS: A total of 24 rats in the single administration group were randomly divided into 5, 10 and 20 mg/kg experimental groups and the control group, with 6 rats in each group. The experimental group was given intraperitoneal injection of MDMA, and the control group was given intraperitoneal injection of the same volume of normal saline as the experimental group. The amount of 0.5 mL blood was collected from the medial canthus 5 min, 30 min, 1 h, 1.5 h, 2 h, 4 h, 6 h, 8 h, 10 h, 12 h after administration. In the continuous administration group, 24 rats were randomly divided into the experimental group (18 rats) and the control group (6 rats). The experimental group was given MDMA 7 d by continuous intraperitoneal injection in increments of 5, 7, 9, 11, 13, 15, 17 mg/kg per day, respectively, while the control group was given the same volume of normal saline as the experimental group by intraperitoneal injection. On the eighth day, the experimental rats were randomly divided into 5, 10 and 20 mg/kg dose groups, with 6 rats in each group. MDMA was injected intraperitoneally, and the control group was injected intraperitoneally with the same volume of normal saline as the experimental group. On the eighth day, 0.5 mL of blood was taken from the medial canthus 5 min, 30 min, 1 h, 1.5 h, 2 h, 4 h, 6 h, 8 h, 10 h, 12 h after administration. Liquid chromatography-triple quadrupole tandem mass spectrometry was used to detect MDMA and MDA levels, and statistical software was employed for data analysis. RESULTS: In the single-administration group, peak concentrations of MDMA and MDA were reached at 5 min and 1 h after administration, respectively, with the largest detection time limit of 12 h. In the continuous administration group, peak concentrations were reached at 30 min and 1.5 h after administration, respectively, with the largest detection time limit of 10 h. Nonlinear fitting equations for the concentration ratio of MDMA and MDA in plasma and administration time in the single-administration group and continuous administration group were as follows: T=10.362C-1.183, R2=0.974 6; T=7.397 3C-0.694, R2=0.961 5 (T: injection time; C: concentration ratio of MDMA to MDA in plasma). CONCLUSIONS: The toxicokinetic data of MDMA and its metabolite MDA in rats, obtained through single and continuous administration, including peak concentration, peak time, detection time limit, and the relationship between concentration ratio and administration time, provide a theoretical and data foundation for relevant forensic identification.


Assuntos
3,4-Metilenodioxianfetamina , Anfetaminas , N-Metil-3,4-Metilenodioxianfetamina , Ratos , Animais , Anfetamina , N-Metil-3,4-Metilenodioxianfetamina/toxicidade , 3,4-Metilenodioxianfetamina/análise , Toxicocinética , Solução Salina
9.
Neuroimage Clin ; 41: 103579, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38447413

RESUMO

In stimulant use and addiction, conflict control processes are crucial for regulating substance use and sustaining abstinence, which can be particularly challenging in social-affective situations. Users of methamphetamine (METH, "Ice") and 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") both experience impulse control deficits, but display different social-affective and addictive profiles. We thus aimed to compare the effects of chronic use of the substituted amphetamines METH and MDMA on conflict control processes in different social-affective contexts (i.e., anger and happiness) and investigate their underlying neurophysiological mechanisms. For this purpose, chronic but recently abstinent users of METH (n = 38) and MDMA (n = 42), as well as amphetamine-naïve healthy controls (n = 83) performed an emotional face-word Stroop paradigm, while event-related potentials (ERPs) were recorded. Instead of substance-specific differences, both MDMA and METH users showed smaller behavioral effects of cognitive-emotional conflict processing (independently of emotional valence) and selective deficits in emotional processing of anger content. Both effects were underpinned by stronger P3 ERP modulations suggesting that users of substituted amphetamines employ altered stimulus-response mapping and decision-making. Given that these processes are modulated by noradrenaline and that both MDMA and METH use may be associated with noradrenergic dysfunctions, the noradrenaline system may underlie the observed substance-related similarities. Better understanding the functional relevance of this currently still under-researched neurotransmitter and its functional changes in chronic users of substituted amphetamines is thus an important avenue for future research.


Assuntos
Metanfetamina , N-Metil-3,4-Metilenodioxianfetamina , Transtornos Relacionados ao Uso de Substâncias , Humanos , N-Metil-3,4-Metilenodioxianfetamina/farmacologia , Metanfetamina/farmacologia , Anfetaminas , Norepinefrina
10.
Neurosci Lett ; 827: 137740, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38521402

RESUMO

New psychoactive substances (NPS) are typically synthesized in clandestine laboratories in an attempt to chemically modify already federally regulated drugs in an effort to circumvent the law. Drugs derived from a phenethylamine pharmacophore, such as 4-chloroamphetamine and 3,4-methylenedioxymethamphetamine (MDMA), reliably induce thermogenesis and serotonergic deficits in the striatum and hippocampus of rodents. 4-methylamphetamine (4-MA), a relative newcomer to the NPS scene, was originally investigated in the mid-1900 s as a potential anorexigenic agent. With its phenethylamine pharmacophore, 4-MA was hypothesized to produce similar toxicological alterations as its chemical analogs. In the present study, three doses (1.0, 2.5, and 5.0 mg/kg, ip.) of 4-MA were administered to rats twice daily for two days. Core temperature data were calculated and analyzed as temperature area under the curve (TAUC). On the second day of dosing, a hypothermic response to 4-MA (2.5 and 5.0 mg/kg) was noted between 0.5 and 2.0 h post-treatment. Only the highest dose of 4-MA decreased body weight on the second day of treatment and maintained this reduction in weight for seven days after treatment ceased. None of the doses of 4-MA evaluated significantly altered serotonin levels in the hippocampus or striatum seven days after final treatment. The present findings demonstrate that the 4-methyl substitution to amphetamine generates a pharmacological and toxicological profile that differs from other similar phenethylamine analogs.


Assuntos
Anfetaminas , Drogas Desenhadas , Metanfetamina , N-Metil-3,4-Metilenodioxianfetamina , Ratos , Animais , Metanfetamina/farmacologia , Serotonina/farmacologia , Drogas Desenhadas/farmacologia , Temperatura , N-Metil-3,4-Metilenodioxianfetamina/farmacologia , Anfetamina/farmacologia , Hipocampo , Serotoninérgicos/farmacologia , Serotoninérgicos/análise
11.
J Pharm Biomed Anal ; 242: 116005, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38364343

RESUMO

The goal of this research is the development of multiple monolithic fiber-solid phase microextraction (MMF-SPME) using a new integrated fiber for the determination of amphetamine derivatives and modafinil from unauthorized medicinal supplements. For this purpose, a monolithic fiber of metal organic framework MIL-Al (53)-deep eutectic solvent (DES)/molecularly imprinted polymers (MOF-DES/MIP) was synthesized. To find optimum microextraction conditions gas chromatography-mass spectrometer (GC-MS) was used and the influences of effective variables were investigated using one factor at a time method. After that, the significant variables were optimized using a Box-Behnken design (BBD) combined with a desirability function (DF). Under optimized conditions (desorption solvent=1500 µL of 1-octanol, pH=3.5, extraction time=35 min, [NaCl]=0% w/v and stirring rate=600 rpm), calibration graphs of analytes were linear in a concentration range of 0.1-400 µg L-1 with correlation coefficients > 0.9966. Limits of detection and quantification were in the ranges of 0.023-0.033 µg L-1 and 0.088-0.113 µg L-1, respectively. This procedure was successfully employed in determining target analytes in spiked and unspiked unauthorized medicinal supplement samples with recoveries ranging from 95.14 to 104.63%.


Assuntos
Estruturas Metalorgânicas , Polímeros Molecularmente Impressos , Polímeros , Modafinila , Microextração em Fase Sólida/métodos , Solventes Eutéticos Profundos , Cromatografia Gasosa-Espectrometria de Massas , Cromatografia Gasosa , Anfetaminas
12.
Forensic Sci Int ; 356: 111966, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38367459

RESUMO

Amphetamine-type stimulants are the third most widely consumed category of illicit drugs worldwide. Faced with the growing problem of amphetamine-type stimulants, numerous qualitative and quantitative techniques have been developed to detect amphetamine (AMP), methamphetamine (MET), MDMA, MDEA or MDA in biological matrices, including hair. Hair analysis is widely used in forensic medicine, but one of its main drawbacks remains external contamination. In this study, we investigated the possibility of hair contamination through external exposure to blood containing AMP, MET MDMA, MDEA or MDA at 2 ng/mL; 20 ng/mL; 200 ng/mL or 2000 ng/mL after 6 h, 1, 3, 7 or 14 days of contact protected from light at room temperature (RT or 20 °C) or at 4 °C. Dried extracts of hair samples were analyzed by UPLC-MS/MS after extensive washings in several baths of water, methanol and acetone before grounding. At the end of our study, contamination of hair was observed from 6 h of contact with all tested amphetamine-type stimulants. The concentrations found in hair ranged from 3 ± 1 to 1464 ± 10 pg/mg, 5 ± 1 to 5070 ± 160 pg/mg, 3 ± 1 to 1269 ± 60 pg/mg, 4 ± 1 to 1860 ± 113 pg/mg and from 8 ± 1 to 1041 ± 44 pg/mg for AMP, MET, MDMA, MDEA and MDA, respectively. Possibly due to its low polar surface area, MET was the most prone to contaminate. As anticipated, hair contamination was mainly dependent on the concentration of all molecules in the contaminating blood, reaching the SOHT cut-off of 200 pg/mg when amphetamine-type stimulants are at toxic or lethal concentrations in the blood. These observations call for caution in interpreting exposure to these substances in such forensic situations.


Assuntos
3,4-Metilenodioxianfetamina/análogos & derivados , Estimulantes do Sistema Nervoso Central , Metanfetamina , N-Metil-3,4-Metilenodioxianfetamina , Anfetaminas/análise , Cromatografia Líquida , Espectrometria de Massas em Tandem , Detecção do Abuso de Substâncias/métodos , Estimulantes do Sistema Nervoso Central/análise , Cabelo/química
13.
J Comp Neurol ; 532(2): e25588, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38335050

RESUMO

Melanin-concentrating hormone (MCH) cells in the hypothalamus regulate fundamental physiological functions like energy balance, sleep, and reproduction. This diversity may be ascribed to the neurochemical heterogeneity among MCH cells. One prominent subpopulation of MCH cells coexpresses cocaine- and amphetamine-regulated transcript (CART), and as MCH and CART can have opposing actions, MCH/CART+ and MCH/CART- cells may differentially modulate behavioral outcomes. However, it is not known if there are differences in the cellular properties underlying their functional differences; thus, we compared the neuroanatomical, electrophysiological, and morphological properties of MCH cells in male and female Mch-cre;L10-Egfp reporter mice. Half of MCH cells expressed CART and were most prominent in the medial hypothalamus. Whole-cell patch-clamp recordings revealed differences in their passive and active membrane properties in a sex-dependent manner. Female MCH/CART+ cells had lower input resistances, but male cells largely differed in their firing properties. All MCH cells increased firing when stimulated, but their firing frequency decreases with sustained stimulation. MCH/CART+ cells showed stronger spike rate adaptation than MCH/CART- cells. The kinetics of excitatory events at MCH cells also differed by cell type, as the rising rate of excitatory events was slower at MCH/CART+ cells. By reconstructing the dendritic arborization of our recorded cells, we found no sex differences, but male MCH/CART+ cells had less dendritic length and fewer branch points. Overall, distinctions in topographical division and cellular properties between MCH cells add to their heterogeneity and help elucidate their response to stimuli or effect on modulating their respective neural networks.


Assuntos
Cocaína , Hormônios Hipotalâmicos , Animais , Feminino , Masculino , Camundongos , Anfetaminas/metabolismo , Hormônios Hipotalâmicos/metabolismo , Hipotálamo/metabolismo , Melaninas/metabolismo , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Neurônios/metabolismo , Hormônios Hipofisários/metabolismo
14.
Environ Res ; 249: 118356, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38331159

RESUMO

Herein, the capture and separation properties of the deep eutectic solvent-functionalized magnetic graphene oxide/ZIF-67 composite (ZMG-DES) towards amphetamine-type drugs (MDMA, MAM and AM) from water were investigated. Kinetic and isotherm models showed that the adsorption behaviors were monolayer chemisorption. Batch experiment results showed that the maximal adsorption of MDMA (933.652 µg⋅g-1) was 2.3 and 2.8 times higher than that of MAM (412.849 µg⋅g-1) and AM (328.652 µg⋅g-1), respectively, and this superiority remained consistent under varied environmental influences (pH, background ion and humic acid). Theoretical calculations and characterization analyses demonstrated the methylenedioxy group of MDMA led to the highly selective adsorption. Electrostatic potential (ESP) distribution indicated that the methylenedioxy added electron-rich areas and provided more adsorption sites. The Independent Gradient Model (IGMH) quantified the adsorption contribution of the functional groups in each system, which the contribution of the methylenedioxy reached 25.23%, significantly exceeding that of -NH- (18.80%) and benzene ring (20.76%), and proved that the H-bonds formed methylenedioxy enhanced adsorption. Furthermore, the Hirshfeld surface analysis proved that the methylenedioxy and -NH- of MDMA acted as H-bond acceptor and donor, respectively, which synergistically promoted the adsorption. The present study will help us to understand the structure-property relationship between amphetamine-type drugs and ZMG-DES.


Assuntos
Grafite , Imidazóis , Poluentes Químicos da Água , Zeolitas , Grafite/química , Adsorção , Poluentes Químicos da Água/química , Poluentes Químicos da Água/análise , Solventes Eutéticos Profundos/química , Anfetaminas/química , Estruturas Metalorgânicas/química , Anfetamina/química , Cinética , Modelos Químicos
15.
Sci Total Environ ; 919: 170473, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38286292

RESUMO

Users of novel psychoactive substances (NPS) are at risk, due to limited information about the toxicity and unpredictable effects of these compounds. Wastewater-based epidemiology (WBE) has been used as a tool to provide insight into NPS use at the population level. To understand the preferences and trends of NPS use in Australia, this study involved liquid chromatography mass spectrometry analysis of wastewater collected from Australian states and territories from February 2022 to February 2023. In total, 59 different NPS were included across two complementary analytical methods and covered up to 57 wastewater catchments over the study. The NPS detected in wastewater were 25-B-NBOMe, buphedrone, 1-benzylpiperazine (BZP), 3-chloromethcathinone, N,N-dimethylpentylone (N,N-DMP), N-ethylheptedrone, N-ethylpentylone, eutylone, 4F-phenibut, 2-fluoro deschloroketamine, hydroxetamine, mephedrone, methoxetamine, methylone, mitragynine, pentylone, phenibut, para-methoxyamphetamine (PMA), alpha-pyrrolidinovalerophenone (α-PVP) and valeryl fentanyl. The detection frequency for these NPS ranged from 3 % to 100 % of the sites analysed. A noticeable decreasing trend in eutylone detection frequency and mass loads was observed whilst simultaneously N,N-DMP and pentylone increased over the study period. The emergence of some NPS in wastewater pre-dates other sources of monitoring and provides further evidence that WBE can be used as an additional early warning system for alerting potential NPS use.


Assuntos
Anfetaminas , Drogas Ilícitas , Vigilância Epidemiológica Baseada em Águas Residuárias , Ácido gama-Aminobutírico/análogos & derivados , Austrália , Águas Residuárias , Drogas Ilícitas/análise , Psicotrópicos/análise
16.
Neurosci Lett ; 823: 137652, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38266975

RESUMO

BACKGROUND: Adderall is a central nervous system stimulant while luteolin has neuroprotective activity. This study aimed to determine whether luteolin can amend neural neurotransmitters, antioxidants, and inflammatory markers in the cerebral cortex of Adderall exposed rats. METHODS: Thirty-six male albino rats were divided into 6 equal groups, Control, Luteolin (1 g/kg)-treated, and Luteolin (2 g/kg)-treated groups: normal rats were orally administrated once a day with 2 ml distilled water, luteolin (1 g/kg), and luteolin (2 g/kg), respectively for 4 weeks. Adderall rats, Adderall rats + luteolin (1 g/kg)-treated, and Adderall rats + luteolin (2 g/kg)-treated groups: normal rats were orally administrated once a day with 10 mg/kg of Adderall, 3 days/week for 4 weeks, then these rats orally administrated daily once a day with 2 ml of distilled water, luteolin (1 g/kg), and luteolin (2 g/kg), respectively for another 4 weeks. RESULTS AND CONCLUSION: Adderall decreased superoxide dismutase, glutathione peroxidase, catalase, NADPH oxidase, interleukin-10, serotonin, dopamine, norepinephrine, γ-aminobutyric acid, and acetylcoline estrase but increased malondialdehyde, conjugated dienes, oxidative index, tumour necrosis factor-α, interleukin-1ß, and interleukin-6 levels in the cerebral cortex. Adderall increased the expression of glial fibrillary acidic protein, ionized calcium binding adaptor molecule 1, and anti-calbindin in the cerebral cortex of Adderall-treated rats. In Adderall-treated rats, daily oral administration of luteolin for 4 weeks brought all these parameters back to values that were close to control where higher dose was more effective than lower dose. The importance of this research is to provide natural compound that amends Adderall-related neural disturbances and this natural compound is cheap, avaliable without any side effect and it does not interfer with Adderall efficiency.


Assuntos
Anfetaminas , Antioxidantes , Luteolina , Ratos , Masculino , Animais , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Luteolina/farmacologia , Ratos Wistar , Córtex Cerebral/metabolismo , Neurotransmissores/farmacologia , Neurotransmissores/metabolismo , Água/farmacologia , Estresse Oxidativo
17.
Subst Use Misuse ; 59(5): 816-824, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38263603

RESUMO

Background: Captagon (Fenethylline) is an amphetamine type stimulant (ATS) and one of the most popular substances of use in the Middle East. This study aims to describe and analyze the trajectory of captagon use, severity of addiction and withdrawal symptoms and its effect on quality of life from the perspectives of people who use captagon, who receive treatment as well as therapists. Methods: This study took a qualitative approach, using semi-structured, audio-recorded interviews, which were transcribed verbatim, translated to English and coded using Nvivo software for thematic analysis. Results: Data saturation was achieved after interviewing a total of 27 participants (7 therapists and 20 patients using captagon either alone or among other illicit drugs), most of which were male (n = 22). Their ages ranged between 18-48 years (median= 27). Four main themes were identified during the interviews: (1) Definition and sought effects of captagon; (2) the downside of captagon use and withdrawal symptoms associated with captagon use; (3) motivations for captagon use and to treatment; and (4) the impact of Covid-19 on captagon's use and on treatment. Conclusion: This qualitative study has illustrated for the first time the several challenges and complicating factors that people who use captagon and therapists face in Jordan. Findings call attention to implementing effective interventions to raise public's awareness of the negative impact of such use, with focus on high-risk groups, address the needs of different users and encourage the use of international treatment guidelines.


Assuntos
Anfetaminas , Qualidade de Vida , Síndrome de Abstinência a Substâncias , Teofilina/análogos & derivados , Humanos , Masculino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Feminino , Jordânia , Anfetamina , Pesquisa Qualitativa
18.
J Psychopharmacol ; 38(3): 236-246, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38279659

RESUMO

BACKGROUND: Dysregulated ventral striatum function has been proposed as one important process occurring in individuals with substance use disorder. This study investigates the role of altered reward and loss anticipation, which is an important component of impaired decision-making, impulsivity, and vulnerability to relapse in individuals with amphetamine use disorder (AMP). AIMS: To determine whether AMP is associated with blunted striatum, prefrontal cortex, and insula signals during win and loss anticipation. METHODS: Participants with and without AMP (AMP+ n = 46, AMP- n = 90) from the Tulsa 1000 study completed a monetary incentive delay (MID) task during functional magnetic resonance imaging. RESULTS: Group main effects indicated that: (1) AMP+ exhibited lower bilateral caudate/putamen and left nucleus accumbens signal than AMP- across anticipation of wins and losses; and (2) AMP+ showed slower reaction times than AMP- during loss anticipation. Group*condition interactions demonstrated that AMP+ exhibited greater right amygdala signal than AMP- while anticipating large wins, a pattern that reversed when anticipating small losses. Left caudate/putamen attenuations in AMP+ during small loss anticipation were also evident. Groups did not differ in prefrontal or insula signals. CONCLUSIONS: AMP+ individuals have altered neural processing and response patterns during reward and loss anticipation, potentially reflecting impairments in dopamine function, which may influence their decision-making and reactions to different win/loss scenarios. These findings help to explain why AMP+ have difficulty with decision-making and exhibit a heightened focus on immediate rewards or punishments.


Assuntos
Transtornos Relacionados ao Uso de Substâncias , Estriado Ventral , Humanos , Recompensa , Motivação , Imageamento por Ressonância Magnética , Estriado Ventral/diagnóstico por imagem , Anfetaminas
19.
Neuropsychopharmacology ; 49(3): 541-550, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37608219

RESUMO

The neuropeptide cocaine- and amphetamine-regulated transcript (CART) has been implicated in alcohol consumption and reward behaviours, yet mechanisms mediating these effects have yet to be identified. Using a transgenic CART knockout (KO) mouse line we uncovered a sexually dimorphic effect of CART in binge drinking, with male CART KO mice increasing intake, whilst female CART KO mice decreased their alcohol intake compared to controls. Female CART KO mice show greater sensitivity to bitter solutions that can be overshadowed through addition of a sweetener, implicating taste as a factor. Further we identify that this is not driven through peripherally circulating sex hormones, but the central nucleus of the amygdala (CeA) is a locus where CART contributes to the regulation of alcohol consumption, with CeA CART neutralisation specifically reducing plain alcohol, but not sweetened alcohol consumption in female mice. These findings may have implications for the development of sex-specific treatment options for alcohol use disorders through targeting the CART system.


Assuntos
Alcoolismo , Consumo Excessivo de Bebidas Alcoólicas , Cocaína , Camundongos , Feminino , Masculino , Animais , Proteínas do Tecido Nervoso/genética , Caracteres Sexuais , Paladar , Consumo Excessivo de Bebidas Alcoólicas/genética , Etanol , Cocaína/farmacologia , Anfetaminas
20.
Int J Drug Policy ; 123: 104279, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38061225

RESUMO

BACKGROUND: Norway aims to eliminate hepatitis C virus (HCV) infection within the end of 2023. Before the introduction of direct-acting antivirals, the prevalence of chronic HCV infection among people who inject drugs (PWID) in Oslo was 40-45 %. The primary aim of the study was to assess changes in HCV prevalence among PWID in Oslo from 2018 to 2021. The secondary aim was to assess change in prevalence in selected subgroups. METHODS: Point prevalence studies were conducted in 2018 and 2021 among PWID attending low-threshold health services in downtown Oslo. Assessments included blood samples analysed for anti-HCV and HCV RNA, and a questionnaire about drug use. Information about previous HCV treatment was only collected in the 2021 cohort. We calculated HCV RNA prevalence estimates for 2018 and 2021 and used logistic regression analysis to identify factors associated with detectable HCV RNA and previous HCV treatment. RESULTS: A total of 281 and 261 participants were included in 2018 and 2021, respectively. The median age was 40.6 and 44.0 years, 73.7 % and 72.8 % were men, and 74.5 % and 78.6 % reported recent (past four weeks) injecting drug use, respectively. HCV RNA prevalence decreased significantly from 26.3 % (95 % CI 21.3-31.9) in 2018 (74 of 281) to 14.2 % (95 % CI 10.2-19.0) in 2021 (37 of 261). The odds of detectable HCV RNA were significantly lower in 2021 compared to 2018 (aOR 0.41; 95 % CI 0.26-0.67). In the 2021 cohort, detectable HCV RNA was associated with recent amphetamine injecting (aOR 7.21; 95 % CI 1.41-36.95), and mixed heroin/amphetamine injecting (aOR 7.97; 95 % CI 1.55-41.07). The odds of previous treatment were lower among women (aOR 0.52; 95 % CI 0.27-1.00). CONCLUSION: A substantial decrease in HCV RNA prevalence among PWID in Oslo between 2018 and 2021 was observed. To reach elimination, adaptive services must be further developed.


Assuntos
Usuários de Drogas , Hepatite C Crônica , Hepatite C , Abuso de Substâncias por Via Intravenosa , Masculino , Humanos , Feminino , Adulto , Hepacivirus/genética , Estudos Transversais , Antivirais/uso terapêutico , Abuso de Substâncias por Via Intravenosa/complicações , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/epidemiologia , Hepatite C Crônica/complicações , Prevalência , Hepatite C/tratamento farmacológico , RNA/uso terapêutico , Anfetaminas
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