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Behavioural Neurology 2015Methamphetamine (METH) is a sympathomimetic amine that belongs to phenethylamine and amphetamine class of psychoactive drugs, which are widely abused for their... (Review)
Review
Methamphetamine (METH) is a sympathomimetic amine that belongs to phenethylamine and amphetamine class of psychoactive drugs, which are widely abused for their stimulant, euphoric, empathogenic, and hallucinogenic properties. Many of these effects result from acute increases in dopamine and serotonin neurotransmission. Subsequent to these acute effects, METH produces persistent damage to dopamine and serotonin release in nerve terminals, gliosis, and apoptosis. This review summarized the numerous interdependent mechanisms including excessive dopamine, ubiquitin-proteasome system dysfunction, protein nitration, endoplasmic reticulum stress, p53 expression, inflammatory molecular, D3 receptor, microtubule deacetylation, and HIV-1 Tat protein that have been demonstrated to contribute to this damage. In addition, the feasible therapeutic strategies according to recent studies were also summarized ranging from drug and protein to gene level.
Topics: Animals; Brain; Dopamine; Endoplasmic Reticulum; Gene Expression; Humans; Methamphetamine; Neurotoxicity Syndromes
PubMed: 25861156
DOI: 10.1155/2015/103969 -
British Journal of Pharmacology Sep 2022Rats emit 50-kHz ultrasonic vocalizations (USV) in appetitive situations, reflecting a positive affective state. Particularly high rates of 50-kHz USV are elicited by... (Review)
Review
Rats emit 50-kHz ultrasonic vocalizations (USV) in appetitive situations, reflecting a positive affective state. Particularly high rates of 50-kHz USV are elicited by the psychostimulant d-amphetamine. Exaggerated 50-kHz USV emission evoked by d-amphetamine is modulated by dopamine, noradrenaline and 5-hydroxytyrptamine receptor ligands and inhibited by the mood stabilizer lithium, the gold standard anti-manic drug for treating bipolar disorder. This indicates that exaggerated 50-kHz USV emission can serve as a reliable and valid measure for assessing mania-like elevated mood in rats with sufficient translational power for gaining a better understanding of relevant pathophysiological mechanisms and the identification of new therapeutic targets. The improved capacity to study the effects of anti-manic pharmacological interventions on a broader range of behaviours by including exaggerated 50-kHz USV emission as preclinical outcome measure complementary to locomotor hyperactivity will refine rodent models for mania. LINKED ARTICLES: This article is part of a themed issue on New discoveries and perspectives in mental and pain disorders. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.17/issuetoc.
Topics: Amphetamine; Animals; Antimanic Agents; Dextroamphetamine; Mania; Rats; Ultrasonics; Vocalization, Animal
PubMed: 33830495
DOI: 10.1111/bph.15487 -
European Annals of Otorhinolaryngology,... Feb 2015Due to their vasoconstrictive action on the nasal mucosa, ephedrine and pseudoephedrine are highly efficient amines for relief of nasal congestion. As with any... (Review)
Review
Due to their vasoconstrictive action on the nasal mucosa, ephedrine and pseudoephedrine are highly efficient amines for relief of nasal congestion. As with any vasoconstrictor and as underscored by the French Society of Otorhinolaryngology in its 2011 guideline, these molecules should not be used in patients under the age of 15. Furthermore, due to unpredictable severe cardiovascular and neurological adverse events that may occur even at low dose and in the absence of any pre-existing pathology, they should not be prescribed for the common cold, and ENT physicians must carefully weigh the risk/benefit ratio in patients with allergic rhinitis. Distribution should be regulated and over-the-counter sales banned.
Topics: Ephedrine; Humans; Nasal Decongestants; Pseudoephedrine; Vasoconstrictor Agents
PubMed: 25532441
DOI: 10.1016/j.anorl.2014.11.001 -
The International Journal of... Aug 2021Synthetic cathinones display overlapping behavioral effects with psychostimulants (e.g., methamphetamine [MA]) and/or entactogens (e.g., 3,4-methylenedioxymethaphetamine...
BACKGROUND
Synthetic cathinones display overlapping behavioral effects with psychostimulants (e.g., methamphetamine [MA]) and/or entactogens (e.g., 3,4-methylenedioxymethaphetamine [MDMA])-presumably reflecting their dopaminergic and/or serotonergic activity. The discriminative stimulus effects of MDMA thought to be mediated by such activity have been well characterized in rodents but have not been fully examined in nonhuman primates.
METHODS
The present studies were conducted to systematically evaluate the discriminative stimulus effects of 5 abused synthetic cathinones (methylenedioxypyrovalerone [MDPV], α-pyrrolidinovalerophenone [α-PVP], methcathinone [MCAT], mephedrone, and methylone) in adult male squirrel monkeys trained to distinguish intramuscular injections of MA (0.1 mg/kg; n = 4) or MDMA (0.6 mg/kg; n = 4) from vehicle.
RESULTS
Each training drug produced dose-dependent effects and, at the highest dose, full substitution. MDMA produced predominantly vehicle-like responding in the MA-trained group, whereas the highest dose of MA (0.56 mg/kg) produced partial substitution (approximately 90% appropriate lever responding in one-half of the subjects) in the MDMA-trained group. MDPV, α-PVP, and MCAT produced full substitution in MA-trained subjects, but, at the same or higher doses, only substituted for MDMA in one-half of the subjects, consistent with primarily dopaminergically mediated interoceptive effects. In contrast, mephedrone and methylone fully substituted in MDMA-trained subjects but failed to fully substitute for the training drug in MA-trained subjects, suggesting a primary role for serotonergic actions in their interoceptive effects.
CONCLUSIONS
These findings suggest that differences in the interoceptive effects of synthetic cathinones in nonhuman primates reflect differing compositions of monoaminergic actions that also may mediate their subjective effects in humans.
Topics: Alkaloids; Animals; Behavior, Animal; Benzodioxoles; Central Nervous System Stimulants; Discrimination Learning; Interoception; Male; Methamphetamine; N-Methyl-3,4-methylenedioxyamphetamine; Propiophenones; Psychotropic Drugs; Pyrrolidines; Saimiri; Synthetic Cathinone
PubMed: 33909067
DOI: 10.1093/ijnp/pyab017 -
Circulation. Cardiovascular Imaging Dec 2018Disease-induced damage to cardiac autonomic nerve populations is associated with an increased risk of sudden cardiac death. The extent of cardiac sympathetic...
BACKGROUND
Disease-induced damage to cardiac autonomic nerve populations is associated with an increased risk of sudden cardiac death. The extent of cardiac sympathetic denervation, assessed using planar scintigraphy or positron emission tomography, has been shown to predict the risk of arrhythmic events in heart failure patients staged for implantable cardioverter defibrillator therapy. The goal of this study was to perform first-in-human evaluations of 4-[F]fluoro-meta-hydroxyphenethylguanidine and 3-[F]fluoro-para-hydroxyphenethylguanidine, 2 new positron emission tomography radiotracers developed for quantifying regional cardiac sympathetic nerve density.
METHODS AND RESULTS
Cardiac positron emission tomography studies with 4-[F]fluoro-meta-hydroxyphenethylguanidine and 3-[F]fluoro-para-hydroxyphenethylguanidine were performed in normal subjects (n=4 each) to assess their imaging properties and organ kinetics. Patlak graphical analysis of their myocardial kinetics was evaluated as a technique for generating nerve density metrics. Whole-body biodistribution studies (n=4 each) were acquired and used to calculate human radiation dosimetry estimates. Patlak analysis proved to be an effective approach for quantifying regional nerve density. Using 960 left ventricular volumes of interest, across-subject Patlak slopes averaged 0.107±0.010 mL/min per gram for 4-[F]fluoro-meta-hydroxyphenethylguanidine and 0.116±0.010 mL/min per gram for 3-[F]fluoro-para-hydroxyphenethylguanidine. Tracer uptake was highest in heart, liver, kidneys, and salivary glands. Urinary excretion was the main elimination pathway.
CONCLUSIONS
4-[F]fluoro-meta-hydroxyphenethylguanidine and 3-[F]fluoro-para-hydroxyphenethylguanidine each produce high-quality positron emission tomography images of the distribution of sympathetic nerves in human heart. Patlak analysis provides reproducible measurements of regional cardiac sympathetic nerve density at high spatial resolution. Further studies of these tracers in heart failure patients will be performed to identify the best agent for clinical development.
CLINICAL TRIAL REGISTRATION
URL: https://www.clinicaltrials.gov . Unique identifier: NCT02385877.
Topics: Adult; Female; Fluorine Radioisotopes; Guanidines; Heart Conduction System; Heart Failure; Humans; Male; Middle Aged; Phenethylamines; Positron-Emission Tomography; Sympathetic Nervous System; Tissue Distribution; Young Adult
PubMed: 30558502
DOI: 10.1161/CIRCIMAGING.118.007965 -
The Analyst May 2021The abuse of methamphetamine (MA) is to date detected and subsequently verified through the monitoring of MA and its metabolites within biological specimens. Current...
The abuse of methamphetamine (MA) is to date detected and subsequently verified through the monitoring of MA and its metabolites within biological specimens. Current approaches require complex sample purification strategies alongside significant analysis time. Given the high prevalence of MA within the global drug market, there remains a need for rapid, portable and alternative screening approaches appropriate for direct detection within biological matrices for employment across the forensic and clinical environments. This contribution illustrates the use of an electrochemiluminescence (ECL) strategy for the screening of MA, amphetamine (AMP) and para hydroxy-methamphetamine (pOH-MA) for such applications. The sensing system showed ideal analytical performance with linear ranges at forensically relevant concentrations of 0.1 μM to 0.5 mM for MA, 10 μM to 1 mM AMP and 10 μM to 5 mM for pOH-MA, and superb detection limits of 74.6 nM, 6 μM and 82. μM for MA, AMP and pOH-MA respectively. Furthermore, the sensor was successful in the detection of MA, AMP and pOH-AMP within human pooled serum, artificial urine and saliva, without any prior purification strategies. Here a portable ECL sensor is detailed for the successful employment of the direct screening of these amphetamine type substances and their corresponding metabolites at clinically and forensically relevant concentrations within a range of biological matrices. This approach successfully represents a strong proof-of-concept, for a novel, simple and rapid screening method with significant potential for high-throughput screening of biological samples for drug metabolites, widening the avenues where ECL sensors could be employed.
Topics: Amphetamine; Humans; Luminescent Measurements; Methamphetamine; Saliva; Substance Abuse Detection
PubMed: 33999061
DOI: 10.1039/d1an00226k -
PloS One 2023Studies that examined the effect of amphetamine or caffeine on spatial working memory (SWM) and verbal working memory (VWM) have used various tasks. However, there are... (Randomized Controlled Trial)
Randomized Controlled Trial
UNLABELLED
Studies that examined the effect of amphetamine or caffeine on spatial working memory (SWM) and verbal working memory (VWM) have used various tasks. However, there are no studies that have used spatial span tasks (SSTs) to assess the SWM effect of amphetamine and caffeine, although some studies have used digit span tasks (DST) to assess VWM. Previous reports also showed that increasing dopamine increases psychosis-like experiences (PLE, or schizotypy) scores which are in turn negatively associated with WM performance in people with high schizotypy and people with schizophrenia. Therefore, the present study aimed to examine the influence of d-amphetamine (0.45 mg/kg, PO), a dopamine releasing stimulant, on SST, DST, and on PLE in healthy volunteers. In a separate study, we examined the effect of caffeine, a nonspecific adenosine receptor antagonist with stimulant properties, on similar tasks.
METHODS
Healthy participants (N = 40) took part in two randomized, double-blind, counter-balanced placebo-controlled cross-over pilot studies: The first group (N = 20) with d-amphetamine (0.45 mg/kg, PO) and the second group (N = 20) with caffeine (200 mg, PO). Spatial span and digit span were examined under four delay conditions (0, 2, 4, 8 s). PLE were assessed using several scales measuring various aspects of psychosis and schizotypy.
RESULTS
We failed to find an effect of d-amphetamine or caffeine on SWM or VWM, relative to placebo. However, d-amphetamine increased a composite score of psychosis-like experiences (p = 0.0005), specifically: Scores on Brief Psychiatric Rating Scale, Perceptual Aberrations Scale, and Magical Ideation Scale were increased following d-amphetamine. The degree of change in PLE following d-amphetamine negatively and significantly correlated with changes in SWM, mainly at the longest delay condition of 8 s (r = -0.58, p = 0.006).
CONCLUSION
The present results showed that moderate-high dose of d-amphetamine and moderate dose of caffeine do not directly affect performances on DST or SST. However, the results indicate that d-amphetamine indirectly influences SWM, through its effect on psychosis-like experiences.
CLINICAL TRIAL REGISTRATION NUMBER
CT-2018-CTN-02561 (Therapeutic Goods Administration Clinical Trial Registry) and ACTRN12618001292268 (The Australian New Zealand Clinical Trials Registry) for caffeine study, and ACTRN12608000610336 for d-amphetamine study.
Topics: Humans; Dextroamphetamine; Caffeine; Healthy Volunteers; Dopamine; Australia; Amphetamine; Double-Blind Method
PubMed: 37440493
DOI: 10.1371/journal.pone.0287538 -
Trends in Pharmacological Sciences Jan 2015In monoaminergic neurons, the vesicular transporters and the plasma membrane transporters operate in a relay. Amphetamine and its congeners target this relay to elicit... (Review)
Review
In monoaminergic neurons, the vesicular transporters and the plasma membrane transporters operate in a relay. Amphetamine and its congeners target this relay to elicit their actions: most amphetamines are substrates, which pervert the relay to elicit efflux of monoamines into the synaptic cleft. However, some amphetamines act as transporter inhibitors. Both compound classes elicit profound psychostimulant effects, which render them liable to recreational abuse. Currently, a surge of new psychoactive substances occurs on a global scale. Chemists bypass drug bans by ingenuous structural variations, resulting in a rich pharmacology. A credible transport model must account for their distinct mode of action and link this to subtle differences in activity and undesired, potentially deleterious effects.
Topics: Amphetamines; Animals; Biological Transport; Humans; Plasma Membrane Neurotransmitter Transport Proteins; Psychotropic Drugs
PubMed: 25542076
DOI: 10.1016/j.tips.2014.11.006 -
Biochemical Pharmacology Dec 2018The use of new psychoactive substituted 2,5-dimethoxy-N-benzylphenethylamines is associated with abuse and toxicity in the United States and elsewhere and their...
The use of new psychoactive substituted 2,5-dimethoxy-N-benzylphenethylamines is associated with abuse and toxicity in the United States and elsewhere and their pharmacology is not well known. This study compares the mechanisms of action of 2-(2,5-dimethoxy-4-methylphenyl)-N-(2-methoxybenzyl)ethanamine (25D-NBOMe), 2-(4-ethyl-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine (25E-NBOMe), 2-(2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine (25H-NBOMe), 2-(((4-iodo-2,5-dimethoxyphenethyl)amino)methyl)phenol (25I-NBOH); and 2-(2,5-dimethoxy-4-nitrophenyl)-N-(2-methoxybenzyl)ethanamine) (25N-NBOMe) with hallucinogens and stimulants. Mammalian cells heterologously expressing 5-HT, 5-HT, 5-HT or 5-HT receptors, or dopamine, serotonin or norepinephrine transporters (DAT, SERT and NET, respectively) were used to assess drug affinities at radioligand binding sites. Potencies and efficacies were determined using [S]GTPγS binding assays (5-HT), inositol-phosphate accumulation assays (5-HT 5-HT and 5-HT), and uptake and release assays (transporters). The substituted phenethylamines were very low potency and low efficacy agonists at the 5-HT receptor. 25D-NBOMe, 25E-NBOMe, 25H-NBOMe, 25I-NBOH and 25N-NBOMe had very high affinity for, and full efficacy at, 5-HT and 5-HT receptors. In the 5-HT receptor functional assay, 25D-NBOMe, 25E-NBOMe, 25I-NBOH and 25N-NBOMe had subnanomolar to low nanomolar potencies similar to (+)lysergic acid diethylamide (LSD) while 25H-NBOMe had lower potency, similar to serotonin. At the 5-HT receptor, four had very high potencies, similar to LSD and serotonin, while 25H-NBOMe had lower potency. At the 5-HT receptor, the compounds had lower affinity, potency and efficacy compared to 5-HT or 5-HT The phenethylamines had low to mid micromolar affinities and potencies at the transporters. These results demonstrate that these -NBOMe and -NBOH substituted phenethylamines have a biochemical pharmacology consistent with hallucinogenic activity, with little psychostimulant activity.
Topics: Dose-Response Relationship, Drug; HEK293 Cells; Humans; Phenethylamines; Psychotropic Drugs; Receptor, Serotonin, 5-HT2A; Serotonin 5-HT2 Receptor Agonists
PubMed: 30261175
DOI: 10.1016/j.bcp.2018.09.024 -
NBOMe: new potent hallucinogens--pharmacology, analytical methods, toxicities, fatalities: a review.European Review For Medical and... Sep 2015NBOMe is a class of emerging new psychoactive substances that has recently gained prominence in the drug abuse market. NBOMes are N-2-methoxy-benzyl substituted 2C class... (Review)
Review
OBJECTIVE
NBOMe is a class of emerging new psychoactive substances that has recently gained prominence in the drug abuse market. NBOMes are N-2-methoxy-benzyl substituted 2C class of hallucinogens, currently being marked online as "research chemicals" under various names: N-bomb, Smiles, Solaris, and Cimbi. This article reviews available literature on the pharmacology; the analytical methods currently used for the detection and quantification of NBOMe in biological matrices and blotters, together with intoxication cases and NBOMe-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 June 2015 using the following keywords: "NBOMe", "Nbomb", "Smiles", "intoxication", "toxicity" "fatalities", "death", "pharmacology", "5-HT2A receptor", "analysis" and "analytical methods". The main key word "NBOMe" was individually searched in association to each of the others.
RESULTS
The review of the literature allowed us to identify 43 citations on pharmacology, analytical methods and NBOMe-related toxicities and fatalities.
CONCLUSIONS
The high potency of NBOMes (potent agonists of 5-HT2A receptor) has led to several severe intoxications, overdose and traumatic fatalities; thus, their increase raises significant public health concerns. Moreover, due to the high potency and ease of synthesis, it is likely that their recreational use will become more widespread in the future. The publication of new data, case reports and evaluation of the NBOMes metabolites is necessary in order to improve knowledge and awareness within the forensic community.
Topics: Benzylamines; Drug Overdose; Hallucinogens; Humans; Phenethylamines; Substance-Related Disorders
PubMed: 26400534
DOI: No ID Found