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Revista de Investigacion Clinica;... 2023This review focuses on the effects and mechanisms of action of amphetamine-type stimulants (ATS) and their adverse effects on the cardiovascular, nervous, and immune... (Review)
Review
This review focuses on the effects and mechanisms of action of amphetamine-type stimulants (ATS) and their adverse effects on the cardiovascular, nervous, and immune systems. ATS include amphetamine (AMPH), methamphetamine (METH, "crystalmeth," or "ice"), methylenedioxymethamphetamine (MDMA, "ecstasy," or "Molly"), MDMA derivatives (e.g., methylenedioxyamphetamine [MDA] and methylenedioxy-N-ethylamphetamine [MDEA]), khat, and synthetic cathinones. The first section of this paper presents an overview of the historical aspects of ATS use, their initial clinical use, and regulations. The second part reviews the acute and chronic impact and the most salient clinical effects of ATS on the central nervous and cardiovascular systems, skin, and mouth. The chemical structure, pharmacokinetics, and classic and non-canonical pharmacological actions are covered in the third section, briefly explaining the mechanisms involved. In addition, the interactions of ATS with the central and peripheral immune systems are reviewed. The last section presents data about the syndemic of ATS and opioid use in the North American region, focusing on the increasing adulteration of METH with fentanyl.
Topics: Humans; Amphetamine; N-Methyl-3,4-methylenedioxyamphetamine; Central Nervous System Stimulants; 3,4-Methylenedioxyamphetamine; Methamphetamine
PubMed: 37441770
DOI: 10.24875/RIC.23000110 -
Current Neuropharmacology 2021The persistence of the addiction phenotype in methamphetamine use disorder (MUD) suggests the potential presence of epigenetic changes and potential structural... (Review)
Review
The persistence of the addiction phenotype in methamphetamine use disorder (MUD) suggests the potential presence of epigenetic changes and potential structural adaptations that may drive the manifestations of MUD in humans. In the present review, we discuss the evidence that documents the fact that methamphetamine exposure can cause changes in epigenetic modifications, including histone acetylation and methylation, as well as DNA methylation and hydroxymethylation in a complex manner that need to be fully dissected. Nevertheless, our work has demonstrated the existence of correlations between behavioral changes and epigenetic alterations during methamphetamine selfadministration. We found that prolonged methamphetamine self-administration and contingent footshocks resulted in rats with compulsive drug-taking and abstinent phenotypes. In addition, rats that reduce their methamphetamine intake in the presence of punishment showed increased DNA hydroxymethylation in genes encoding potassium channels in their nucleus accumbens. Moreover, altered DNA hydroxymethylation in those genes led to an increase in their mRNA expression. Additional studies revealed decreased mRNA expression of histone deacetylases associated with increased histone acetylation and induced gene expression in the dorsal striatum. These changes were associated with a reduction in methamphetamine intake in response to contingent footshocks. More research is necessary in order to further dissect how pharmacological or genetic manipulations of identified epigenetic alterations and expression of potassium channels can impact methamphetamine-taking behaviors or relapse to methamphetamine-taking after long periods of abstinence. Investigations that use discovery approaches, such as whole-genome sequencing after chromatin immunoprecipitation, should accelerate our efforts to develop epigenetic therapeutic approaches against MUD.
Topics: Acetylation; Animals; DNA Methylation; Epigenesis, Genetic; Methamphetamine; Nucleus Accumbens; Rats
PubMed: 34030618
DOI: 10.2174/1570159X19666210524111915 -
International Journal of Molecular... Mar 2023According to the EU Early Warning System (EWS), synthetic cathinones (SCs) are the second largest new psychoactive substances (NPS) class, with 162 synthetic cathinones... (Review)
Review
According to the EU Early Warning System (EWS), synthetic cathinones (SCs) are the second largest new psychoactive substances (NPS) class, with 162 synthetic cathinones monitored by the EU EWS. They have a similar structure to cathinone, principally found in Catha Edulis; they have a phenethylamine related structure but also exhibit amphetamine-like stimulant effects. Illegal laboratories regularly develop new substances and place them on the market. For this reason, during the last decade this class of substances has presented a great challenge for public health and forensic toxicologists. Acting on different systems and with various mechanisms of action, the spectrum of side effects caused by the intake of these drugs of abuse is very broad. To date, most studies have focused on the substances' cardiac effects, and very few on their associated neurotoxicity. Specifically, synthetic cathinones appear to be involved in different neurological events, including increased alertness, mild agitation, severe psychosis, hyperthermia and death. A systematic literature search in PubMed and Scopus databases according to PRISMA guidelines was performed. A total of 515 studies published from 2005 to 2022 (350 articles from PubMed and 165 from Scopus) were initially screened for eligibility. The papers excluded, according to the criteria described in the Method Section (n = 401) and after full text analyses (n = 82), were 483 in total. The remaining 76 were included in the present review, as they met fully the inclusion criteria. The present work provides a comprehensive review on neurotoxic mechanisms of synthetic cathinones highlighting intoxication cases and fatalities in humans, as well as the toxic effects on animals (in particular rats, mice and zebrafish larvae). The reviewed studies showed brain-related adverse effects, including encephalopathy, coma and convulsions, and sympathomimetic and hallucinogenic toxidromes, together with the risk of developing excited/agitated delirium syndrome and serotonin syndrome.
Topics: Mice; Rats; Humans; Animals; Synthetic Cathinone; Zebrafish; Central Nervous System Stimulants; Fever; Amphetamine; Neurotoxicity Syndromes; Psychotropic Drugs
PubMed: 37047201
DOI: 10.3390/ijms24076230 -
Journal of the American Pharmacists... 2021Adderall (amphetamine-dextroamphetamine) is a controlled substance with harmful adverse effects if abused or misused. We assessed the availability of Adderall from...
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.
Topics: Amphetamines; Controlled Substances; Cross-Sectional Studies; Humans; Internet; Pharmaceutical Services, Online; Pharmacies
PubMed: 32912756
DOI: 10.1016/j.japh.2020.07.022 -
Brain, Behavior and Evolution 2020Phenethylamines (e.g., methamphetamine) are a common source of drug toxicity. Phenethylamine-induced hyperthermia (PIH) can activate a cascade of events that may result... (Review)
Review
Phenethylamines (e.g., methamphetamine) are a common source of drug toxicity. Phenethylamine-induced hyperthermia (PIH) can activate a cascade of events that may result in rhabdomyolysis, coagulopathy, and even death. Here, we review recent evidence that suggests a potential link between the gut-brain axis and PIH. Within the preoptic area of the hypothalamus, phenethylamines lead to changes in catecholamine levels, that activate the sympathetic nervous system (SNS) and increase the peripheral levels of norepinephrine (NE), resulting in: (1) the loss of heat dissipation through α1 adrenergic receptor (α1-AR)-mediated vasoconstriction, (2) heat generation through β-AR activation and subsequent free fatty acid (FFA) activation of uncoupling proteins (UCPs) in brown and white adipose tissue, and (3) alteration of the gut microbiome and its link to the gut-brain axis. Recent studies have shown that phenethylamine derivatives can influence the composition of the gut microbiome and thus its metabolic potential. Phenethylamines increase the relative level of Proteuswhich has been linked to enhanced NE turnover. Bidirectional fecal microbial transplants (FMT) between PIH-tolerant and PIH-naïve rats demonstrated that the transplantation of gut microbiome can confer phenotypic hyperthermic and tolerant responses to phenethylamines. These phenethylamine-mediated changes in the gut microbiome were also associated with epigenetic changes in the mediators of thermogenesis. Given the significant role that the microbiome has been shown to play in the maintenance of body temperature, we outline current studies demonstrating the effects of phenethylamines on the gut microbiome and how these microbiome changes may mechanistically contribute to alterations in body temperature.
Topics: Animals; Gastrointestinal Microbiome; Hyperthermia; Phenethylamines; Rats; Thermogenesis
PubMed: 33472193
DOI: 10.1159/000512098 -
Scientific Reports Nov 2023Monoamine oxidase B (MAO-B) inhibitors are used to control Parkinson's disease (PD). Selegiline, rasagiline, and safinamide are widely used as MAO-B inhibitors...
Monoamine oxidase B (MAO-B) inhibitors are used to control Parkinson's disease (PD). Selegiline, rasagiline, and safinamide are widely used as MAO-B inhibitors worldwide. Although these drugs inhibit MAO-B, there are pharmacological and chemical differences, such as the inhibitory activity, the non-dopaminergic properties in safinamide, and the amphetamine-like structure in selegiline. MAO-B inhibitors may differ in adverse events (AEs). However, differences in actual practical clinics are not fully investigated. A retrospective study was conducted using FAERS, the largest database of spontaneous adverse events. AE signals for MAO-B inhibitors, including selegiline, rasagiline, and safinamide, were detected using the reporting odds ratio method and compared. Hypocomplementemia, hepatic cyst, hepatic function abnormal, liver disorder and cholangitis were detected for selegiline as drug-specific signals. The amphetamine effect was not confirmed for any of the three MAO-B inhibitors. The tyramine reaction was detected as an AE signal only for rasagiline. Moreover, the REM sleep behavior disorder was not detected as an AE signal for safinamide, suggesting that non-dopaminergic effects might be beneficial. Considering the differences in AEs for MAO-B inhibitors will assist with the appropriate PD medication.
Topics: Humans; Monoamine Oxidase Inhibitors; Parkinson Disease; Selegiline; Retrospective Studies; Monoamine Oxidase; Dopamine Agents; Amphetamines
PubMed: 37935702
DOI: 10.1038/s41598-023-44142-2 -
Journal of Medicinal Chemistry Aug 2023The cardiotoxicity associated with -ethyl-dexfenfluramine (norDF) and related agonists of the serotonin receptor 2B (5-HT) has solidified the receptor's place as an... (Review)
Review
The cardiotoxicity associated with -ethyl-dexfenfluramine (norDF) and related agonists of the serotonin receptor 2B (5-HT) has solidified the receptor's place as an "antitarget" in drug discovery. Conversely, a growing body of evidence has highlighted the utility of 5-HT antagonists for the treatment of pulmonary arterial hypertension (PAH), valvular heart disease (VHD), and related cardiopathies. In this Perspective, we summarize the link between the clinical failure of fenfluramine-phentermine (fen-phen) and the subsequent research on the role of 5-HT in disease progression, as well as the development of drug-like and receptor subtype-selective 5-HT antagonists. Such agents represent a promising class for the treatment of PAH and VHD, but their utility has been historically understudied due to the clinical disasters associated with 5-HT. Herein, it is our aim to examine the current state of 5-HT drug discovery, with an emphasis on the receptor's role in the central nervous system (CNS) versus the periphery.
Topics: Humans; Receptor, Serotonin, 5-HT2B; Serotonin; Fenfluramine; Heart Valve Diseases; Drug Discovery
PubMed: 37584406
DOI: 10.1021/acs.jmedchem.3c01178 -
Journal of Forensic Sciences Mar 2020
Topics: Amphetamines; Cocaine; Humans; Ketamine; Opiate Alkaloids; Substance-Related Disorders
PubMed: 31995236
DOI: 10.1111/1556-4029.14273 -
Emergencias : Revista de La Sociedad...
Topics: Amphetamine; Emergency Service, Hospital; Hospitals; Humans; Laboratories; Methamphetamine
PubMed: 32692020
DOI: No ID Found -
Revista Brasileira de Psiquiatria (Sao... 2021
Topics: Combined Modality Therapy; Humans; N-Methyl-3,4-methylenedioxyamphetamine; Psychotherapy; Stress Disorders, Post-Traumatic
PubMed: 33053043
DOI: 10.1590/1516-4446-2020-0020