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JACC. Clinical Electrophysiology Dec 2016
Topics: Anti-Arrhythmia Agents; Phenethylamines; Sulfonamides
PubMed: 29759760
DOI: 10.1016/j.jacep.2016.06.005 -
Current Molecular Pharmacology 2019Mescaline (3,4,5-trimethoxyphenethylamine), mainly found in the Peyote cactus (Lophophora williamsii), is one of the oldest known hallucinogenic agents that influence... (Review)
Review
BACKGROUND
Mescaline (3,4,5-trimethoxyphenethylamine), mainly found in the Peyote cactus (Lophophora williamsii), is one of the oldest known hallucinogenic agents that influence human and animal behavior, but its psychoactive mechanisms remain poorly understood.
OBJECTIVES
This article aims to fully review pharmacokinetics and pharmacodynamics of mescaline, focusing on the in vivo and in vitro metabolic profile of the drug and its implications for the variability of response.
METHODS
Mescaline pharmacokinetic and pharmacodynamic aspects were searched in books and in PubMed (U.S. National Library of Medicine) without a limiting period. Biological effects of other compounds found in peyote were also reviewed.
RESULTS
Although its illicit administration is less common, in comparison with cocaine and Cannabis, it has been extensively described in adolescents and young adults, and licit consumption often occurs in religious and therapeutic rituals practiced by the Native American Church. Its pharmacodynamic mechanisms of action are primarily attributed to the interaction with the serotonergic 5-HT2A-C receptors, and therefore clinical effects are similar to those elicited by other psychoactive substances, such as lysergic acid diethylamide (LSD) and psilocybin, which include euphoria, hallucinations, depersonalization and psychoses. Moreover, as a phenethylamine derivative, signs and symptoms are consistent with a sympathomimetic effect. Mescaline is mainly metabolized into trimethoxyphenylacetic acid by oxidative deamination but several minor metabolites with possible clinical and forensic repercussions have also been reported.
CONCLUSION
Most reports concerning mescaline were presented in a complete absence of exposure confirmation, since toxicological analysis is not widely available. Addiction and dependence are practically absent and it is clear that most intoxications appear to be mild and are unlikely to produce lifethreatening symptoms, which favors the contemporary interest in the therapeutic potential of the drugs of the class.
Topics: Animals; Cactaceae; Forensic Medicine; Hallucinogens; Humans; Intestinal Absorption; Mescaline; Tissue Distribution
PubMed: 30318013
DOI: 10.2174/1874467211666181010154139 -
Emergencias : Revista de La Sociedad...
Topics: Amphetamine; Emergency Service, Hospital; Hospitals; Humans; Laboratories; Methamphetamine
PubMed: 32692020
DOI: No ID Found -
International Journal of Molecular... Aug 2022Dofetilide is a rapid delayed rectifier potassium current inhibitor widely used to prevent the recurrence of atrial fibrillation and flutter. The clinical use of this...
Dofetilide is a rapid delayed rectifier potassium current inhibitor widely used to prevent the recurrence of atrial fibrillation and flutter. The clinical use of this drug is associated with increases in QTc interval, which predispose patients to ventricular cardiac arrhythmias. The mechanisms involved in the disposition of dofetilide, including its movement in and out of cardiomyocytes, remain unknown. Using a xenobiotic transporter screen, we identified MATE1 () as a transporter of dofetilide and found that genetic knockout or pharmacological inhibition of MATE1 in mice was associated with enhanced retention of dofetilide in cardiomyocytes and increased QTc prolongation. The urinary excretion of dofetilide was also dependent on the MATE1 genotype, and we found that this transport mechanism provides a mechanistic basis for previously recorded drug-drug interactions of dofetilide with various contraindicated drugs, including bictegravir, cimetidine, ketoconazole, and verapamil. The translational significance of these observations was examined with a physiologically-based pharmacokinetic model that adequately predicted the drug-drug interaction liabilities in humans. These findings support the thesis that MATE1 serves a conserved cardioprotective role by restricting excessive cellular accumulation and warrant caution against the concurrent administration of potent MATE1 inhibitors and cardiotoxic substrates with a narrow therapeutic window.
Topics: Animals; Anti-Arrhythmia Agents; Atrial Fibrillation; Humans; Mice; Phenethylamines; Sulfonamides
PubMed: 35955741
DOI: 10.3390/ijms23158607 -
Attention-Deficit/Hyperactivity Disorder Medications and Work Disability and Mental Health Outcomes.JAMA Network Open Mar 2024Individuals with attention-deficit/hyperactivity disorder (ADHD) often have comorbid psychiatric conditions. Relatively little is known about how specific ADHD...
IMPORTANCE
Individuals with attention-deficit/hyperactivity disorder (ADHD) often have comorbid psychiatric conditions. Relatively little is known about how specific ADHD medications are associated with overall treatment outcomes among these patients.
OBJECTIVE
To investigate the association of the use of specific ADHD medications with hospitalization outcomes and work disability among adolescents and adults with ADHD.
DESIGN, SETTING, AND PARTICIPANTS
This nationwide register-based cohort study identified individuals (aged 16-65 years) with ADHD from Swedish nationwide registers of inpatient health care, specialized outpatient health care, sickness absence, and disability pension during the years 2006 to 2021. Data analysis was performed from November 2022 to August 2023.
EXPOSURE
Use of specific ADHD medications.
MAIN OUTCOMES AND MEASURES
The main outcome measure was psychiatric hospitalization, and secondary outcomes were suicide attempt and/or death by suicide, nonpsychiatric hospitalization, and work disability (ie, sickness absence or disability pension). The risk of outcomes between use vs nonuse periods of ADHD medications was compared in a within-individual design, where a person acts as their own control, and was analyzed with stratified Cox models.
RESULTS
A total of 221 714 persons with ADHD were included in the study cohort (mean [SD] age, 25.0 [11.2] years; 120 968 male individuals [54.6%]). Methylphenidate was the most commonly used ADHD medication (151 837 individuals [68.5%]), followed by lisdexamphetamine (78 106 individuals [35.2%]) during the follow-up (mean [SD], 7.0 [4.7] years). The following medications were associated with a decreased risk of psychiatric hospitalization: amphetamine (adjusted hazard ratio [aHR], 0.74; 95% CI, 0.61-0.90), lisdexamphetamine (aHR, 0.80; 95% CI, 0.78-0.82), ADHD drug polytherapy (aHR, 0.85; 95% CI, 0.82-0.88), dexamphetamine (aHR, 0.88; 95% CI, 0.83-0.94), and methylphenidate (aHR, 0.93; 95% CI, 0.92-0.95). No associations were found for modafinil, atomoxetine, clonidine, and guanfacine. Decreased risk of suicidal behavior was associated with the use of dexamphetamine (aHR, 0.69; 95% CI, 0.53-0.89), lisdexamphetamine (aHR, 0.76; 95% CI, 0.68-0.84), and methylphenidate (aHR, 0.92; 95% CI, 0.86-0.98). None of the medications was associated with increased risk of nonpsychiatric hospitalization; instead, use of amphetamine, lisdexamphetamine, polytherapy, dexamphetamine, methylphenidate, and atomoxetine were associated with decreased risk of nonpsychiatric hospitalization. The results regarding work disability were significant only for the use of atomoxetine (aHR, 0.89; 95% CI, 0.82-0.97), especially among adolescents and young adults aged 16 to 29 years, (aHR, 0.82; 95% CI, 0.73-0.92).
CONCLUSIONS AND RELEVANCE
In this nationwide cohort study of adolescents and adults with ADHD, the use of ADHD medication was associated with fewer hospitalizations for both psychiatric and nonpsychiatric morbidity and lower suicidal behavior.
Topics: Adolescent; Young Adult; Humans; Male; Adult; Attention Deficit Disorder with Hyperactivity; Atomoxetine Hydrochloride; Cohort Studies; Lisdexamfetamine Dimesylate; Methylphenidate; Amphetamine
PubMed: 38506810
DOI: 10.1001/jamanetworkopen.2024.2859 -
Biological Psychiatry Jun 2019Disruptions in the decision-making processes that guide action selection are a core feature of many psychiatric disorders, including addiction. Decision making is...
BACKGROUND
Disruptions in the decision-making processes that guide action selection are a core feature of many psychiatric disorders, including addiction. Decision making is influenced by the goal-directed and habitual systems that can be computationally characterized using model-based and model-free reinforcement learning algorithms, respectively. Recent evidence suggests an imbalance in the influence of these reinforcement learning systems on behavior in individuals with substance dependence, but it is unknown whether these disruptions are a manifestation of chronic drug use and/or are a preexisting risk factor for addiction.
METHODS
We trained adult male rats on a multistage decision-making task to quantify model-free and model-based processes before and after self-administration of methamphetamine or saline.
RESULTS
Individual differences in model-free, but not model-based, learning prior to any drug use predicted subsequent methamphetamine self-administration; rats with lower model-free behavior took more methamphetamine than rats with higher model-free behavior. This relationship was selective to model-free updating following a rewarded, but not unrewarded, choice. Both model-free and model-based learning were reduced in rats following methamphetamine self-administration, which was due to a decrement in the ability of rats to use unrewarded outcomes appropriately. Moreover, the magnitude of drug-induced disruptions in model-free learning was not correlated with disruptions in model-based behavior, indicating that drug self-administration independently altered both reinforcement learning strategies.
CONCLUSIONS
These findings provide direct evidence that model-free and model-based learning mechanisms are involved in select aspects of addiction vulnerability and pathology, and they provide a unique behavioral platform for conducting systems-level analyses of decision making in preclinical models of mental illness.
Topics: Animals; Behavior, Addictive; Decision Making; Male; Methamphetamine; Models, Psychological; Rats; Reinforcement, Psychology
PubMed: 30737015
DOI: 10.1016/j.biopsych.2018.12.017 -
Drug Design, Development and Therapy 2014Recent studies have promised that lisdexamfetamine (LDX) is effective in the treatment of adults with attention-deficit hyperactivity disorder (ADHD). (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Recent studies have promised that lisdexamfetamine (LDX) is effective in the treatment of adults with attention-deficit hyperactivity disorder (ADHD).
OBJECTIVES
This systematic review was undertaken to summarize LDX efficacy, acceptability, and tolerability in adult ADHD. All randomized controlled trials (RCTs) of lisdexamfetamine compared with placebo were included for synthesis. Clinical trials published between January 1991 and January 2014 were evaluated.
METHODS
The database of MEDLINE(®), EMBASE™, CINAHL(®), PsycINFO(®) and Cochrane Controlled Trials Register were searched in January 2014. Studies were also searched in ClinicalTrials.gov and the EU Clinical Trials Register database. Study eligibility criteria, participants, and interventions were considered. All RCTs of LDX vs placebo reporting final results of: 1) severity of ADHD symptoms and executive function deficit, 2) response or remission rates, 3) overall discontinuation rate, or 4) discontinuation rate due to adverse events were included. The language of the papers was not restricted. All abstracts of studies gathered from the database were examined. After excluding irrelevant trials, the full text version of relevant studies were assessed and extracted for outcomes of interest. Examination of risks of bias, based on the Cochrane bias assessment, was carried out. The efficacy outcomes consisted of the mean end point or change scores for ADHD rating scales, the response rate, and the remission rate. The overall discontinuation rate and the discontinuation rate due to adverse events were measured for acceptability and tolerability, respectively. A random effect model was applied for the synthesis of relative risks (RRs), and weighted mean differences or standardized mean differences (SMDs) with 95% confidence intervals (CIs).
RESULTS
A total of 806 final study or safety participants were included. The dosage of lisdexamfetamine was 30 to 70 mg/day. The pooled mean scores of mean change and mean end point scores between LDX- and placebo-treated groups also had a significant difference (SMD [95% CI] of -0.97 [-1.15, -0.78], I(2)=18%). The pooled response rates for adult ADHD between the two groups had a significant difference (RR [95% CI] of 1.99 [1.50, 2.63], I(2)=0%). Based on the Behavior Rating Inventory of Executive Function - Adult version (BRIEF-A), the pooled end point mean scores for the Global Executive Composite (GEC) for the LDX-treated groups was greater than that of placebo-treated groups (MD [95% CI] of -9.20 [-14.11, -4.29], I(2)=34%). The pooled overall discontinuation rates between the two groups had no significant difference (RR [95% CI] of 0.82 [0.59, 1.14], I(2)=0%). Similarly, the pooled discontinuation rates due to adverse events between the two groups was not significantly different (RR [95% CI] of 1.77 [0.71, 4.40], I(2)=0%).
CONCLUSION
The number of included studies was limited (five RCTs), but based on this meta-analysis, LDX is efficacious and well tolerated in the treatment of adult ADHD. Additionally, it also improved the executive function deficits in this population. However, its acceptability is no higher than placebo. These findings should be carefully interpreted and considered as preliminary outcomes. To confirm these results, further studies are warranted. LDX is a viable alternative psychostimulant for adult ADHD.
Topics: Attention Deficit Disorder with Hyperactivity; Databases, Factual; Dextroamphetamine; Humans; Lisdexamfetamine Dimesylate; Placebos; Registries
PubMed: 25336914
DOI: 10.2147/DDDT.S68393 -
International Journal of Environmental... Nov 2019Contamination of residential homes with methamphetamine is an emerging issue of significant concern to public health. Cooking or smoking methamphetamine in a residential... (Review)
Review
Contamination of residential homes with methamphetamine is an emerging issue of significant concern to public health. Cooking or smoking methamphetamine in a residential property contaminates the house, furnishings and personal possessions within it, with subsequent exposure through ingestion, dermal absorption and/or inhalation causing adverse health effects. Current guidelines identifying levels of methamphetamine contamination that require remediation vary between countries. There is also no international standard protocol for measuring levels of contamination and research has shown that different materials give rise to different recovery rates of methamphetamine. There are a number of currently used remediation methods; however, they have varying levels of success with limited studies comparing their long-term efficacies. Most importantly, there are few guidelines available that are based on a transparent, health risk-based approach, and there are many uncertainties on exposures and health effects, making it difficult to ensure the health of people residing in homes that have been used to cook or smoke methamphetamine are sufficiently protected. This manuscript presents the current state of knowledge regarding the contamination of residential homes with methamphetamine and identifies the current gaps in knowledge and priority areas for future research. The current regulatory approach to public health protection associated with exposure to residential premises contaminated with methamphetamine in Australia, New Zealand and the USA is also discussed.
Topics: Environmental Pollutants; Humans; Methamphetamine; Public Health; Substance-Related Disorders
PubMed: 31771211
DOI: 10.3390/ijerph16234676 -
Forensic Toxicology Jan 2023The present review aims to provide an overview of methods for the quantification of 2,5-dimethoxy-amphetamines and -phenethylamines in different biological matrices,... (Review)
Review
PURPOSE
The present review aims to provide an overview of methods for the quantification of 2,5-dimethoxy-amphetamines and -phenethylamines in different biological matrices, both traditional and alternative ones.
METHODS
A complete literature search was carried out with PubMed, Scopus and the World Wide Web using relevant keywords, e.g., designer drugs, amphetamines, phenethylamines, and biological matrices.
RESULTS
Synthetic phenethylamines represent one of the largest classes of "designer drugs", obtained through chemical structure modifications of psychoactive substances to increase their pharmacological activities. This practice is also favored by the fact that every new synthetic compound is not considered illegal by existing legislation. Generally, in a toxicological laboratory, the first monitoring of drugs of abuse is made by rapid screening tests that sometimes can occur in false positive or false negative results. To reduce evaluation errors, it is mandatory to submit the positive samples to confirmatory methods, such as gas chromatography or liquid chromatography combined to mass spectrometry, for a more specific qualitative and quantitative analysis.
CONCLUSIONS
This review highlights the great need for updated comprehensive analytical methods, particularly when analyzing biological matrices, both traditional and alternative ones, for the search of newly emerging designer drugs.
Topics: Phenethylamines; Gas Chromatography-Mass Spectrometry; Amphetamines; Mass Spectrometry; Chromatography, Liquid
PubMed: 36652064
DOI: 10.1007/s11419-022-00638-6 -
European Review For Medical and... Oct 2015Synthetic cathinones are an emerging class of designer drugs abused of due to their psychostimulant and hallucinogenic effects, similar to those of cocaine,... (Review)
Review
OBJECTIVE
Synthetic cathinones are an emerging class of designer drugs abused of due to their psychostimulant and hallucinogenic effects, similar to those of cocaine, methylenedioxymethamphetamine (MDMA), amphetamines and methamphetamines. Mephedrone is a cathinone analogue (4-methyl aromatic analogue of methcathinone) that was reported to be implicated in several fatalities in the media across Europe, but only a few have actually resulted in mephedrone cited as the cause of death. In this paper, we aim to systematically review analytically confirmed cases of mephedrone-related fatalities.
MATERIALS AND METHODS
Relevant scientific articles were identified from Medline, Cochrane Central, Scopus, Web of Science, Science Direct, EMBASE and Google Scholar, through May 2015 using the following keywords: "Mephedrone", "fatal intoxication," "fatalities", "acute intoxication" and "death".
RESULTS
In total, 10 citations met the criteria for inclusion, representing 18 fatal cases with analytically confirmed mephedrone in biological sample/s of the deceased. The death was attributed to mephedrone intoxication in 9 cases (range of post-mortem blood mephedrone concentration: 1.33-22 mg/L), whereas multiple drug toxicity, involving mephedrone was cited as cause of death in 6 cases (range of post-mortem blood mephedrone concentration: 0.04-1.3 mg/L).
CONCLUSIONS
Data suggest that the abuse of mephedrone remains to be a public health issue. Mephedrone appears to have a rather narrow therapeutic window that makes its use dangerous. Dosages which supposedly fall within recreational use limits could also lead to death when combined with other drugs in certain circumstances. Forensic Toxicology laboratories must assess their testing procedures to ensure they can achieve both an appropriate screening regime and targeted quantitative analysis for the detection of mephedrone in various biological matrices.
Topics: Alkaloids; Central Nervous System Stimulants; Death; Designer Drugs; Humans; Methamphetamine; Substance-Related Disorders
PubMed: 26502870
DOI: No ID Found