-
Emergency Medicine Clinics of North... Aug 2021In recent years, there has been an emergence of numerous novel drugs. Such toxicity may occur in both adolescents and adults. This article discusses the opioid epidemic... (Review)
Review
In recent years, there has been an emergence of numerous novel drugs. Such toxicity may occur in both adolescents and adults. This article discusses the opioid epidemic and several emerging opioids, including buprenorphine, loperamide, fentanyl, fentanyl derivatives, and others. Kratom, a plant occasionally used for opiate detoxification, along with the sedatives etizolam and phenibut, will be discussed. Lastly, this article discusses the phenethylamines and marijuana.
Topics: Analgesics, Opioid; Buprenorphine; Cannabinoids; Designer Drugs; Drug Overdose; Fentanyl; Humans; Hypnotics and Sedatives; Illicit Drugs; Loperamide; Mitragyna; Naloxone; Narcotic Antagonists; Phenethylamines; Substance-Related Disorders
PubMed: 34215409
DOI: 10.1016/j.emc.2021.04.013 -
Journal of Psychopharmacology (Oxford,... May 2021
Topics: Humans; N-Methyl-3,4-methylenedioxyamphetamine; Psychotherapy; Substance-Related Disorders
PubMed: 33938311
DOI: 10.1177/02698811211012604 -
The American Journal of Drug and... Sep 2023A drug concoction called tusi has emerged in Latin America and in Europe and is now beginning to acquire popularity in the United States. "Tusi" is a phonetic...
A drug concoction called tusi has emerged in Latin America and in Europe and is now beginning to acquire popularity in the United States. "Tusi" is a phonetic translation of "2C," a series of psychedelic phenethylamines. The concoction is also sometimes referred to as "pink cocaine" as it typically comes in the form of pink powder. However, despite its name, the concoction rarely contains 2C series drugs. Multiple drug checking studies have found that the majority of tusi samples contain ketamine, often combined with 3,4-methylenedioxymethamphetamine (MDMA), methamphetamine, cocaine, opioids, and/or new psychoactive substances. The tusi phenomenon complicates the drug landscape because it has the potential to confuse both people who use it and researchers alike. People using may think the drug is 2C/2C-B, and they may also be unaware that the concoction tends to consist of ketamine and a wide variety of other drugs. Unintentional exposure to its contents can lead to increased risk of adverse effects. The tusi phenomenon also has the potential to complicate drug research as unknown exposure to drugs like ketamine and MDMA will lead to underreporting of use. A combination of self-report and toxicological testing may be needed to inform the most accurate estimates of use. Both researchers and people at risk for use need to be informed about this new concoction. Drug researchers need to be cognizant about the way they query use, and people at risk for using need to be educated about the possible contents of tusi and associated dangers.
Topics: Humans; N-Methyl-3,4-methylenedioxyamphetamine; Ketamine; Hallucinogens; Methamphetamine; Cocaine; Substance-Related Disorders
PubMed: 37162319
DOI: 10.1080/00952990.2023.2207716 -
Nature Dec 2023Trace amine-associated receptor 1 (TAAR1), the founding member of a nine-member family of trace amine receptors, is responsible for recognizing a range of biogenic...
Trace amine-associated receptor 1 (TAAR1), the founding member of a nine-member family of trace amine receptors, is responsible for recognizing a range of biogenic amines in the brain, including the endogenous β-phenylethylamine (β-PEA) as well as methamphetamine, an abused substance that has posed a severe threat to human health and society. Given its unique physiological role in the brain, TAAR1 is also an emerging target for a range of neurological disorders including schizophrenia, depression and drug addiction. Here we report structures of human TAAR1-G-protein complexes bound to methamphetamine and β-PEA as well as complexes bound to RO5256390, a TAAR1-selective agonist, and SEP-363856, a clinical-stage dual agonist for TAAR1 and serotonin receptor 5-HTR (refs. ). Together with systematic mutagenesis and functional studies, the structures reveal the molecular basis of methamphetamine recognition and underlying mechanisms of ligand selectivity and polypharmacology between TAAR1 and other monoamine receptors. We identify a lid-like extracellular loop 2 helix/loop structure and a hydrogen-bonding network in the ligand-binding pockets, which may contribute to the ligand recognition in TAAR1. These findings shed light on the ligand recognition mode and activation mechanism for TAAR1 and should guide the development of next-generation therapeutics for drug addiction and various neurological disorders.
Topics: Humans; Ligands; Methamphetamine; Nervous System Diseases; Phenethylamines; Receptors, G-Protein-Coupled; Substance-Related Disorders; Heterotrimeric GTP-Binding Proteins; Polypharmacology; Hydrogen Bonding
PubMed: 37935377
DOI: 10.1038/s41586-023-06775-1 -
Nature Communications Aug 2023The incidence of metabolic syndrome is significantly higher in patients with irritable bowel syndrome (IBS), but the mechanisms involved remain unclear. Gut microbiota...
The incidence of metabolic syndrome is significantly higher in patients with irritable bowel syndrome (IBS), but the mechanisms involved remain unclear. Gut microbiota is causatively linked with the development of both metabolic dysfunctions and gastrointestinal disorders, thus gut dysbiosis in IBS may contribute to the development of metabolic syndrome. Here, we show that human gut bacterium Ruminococcus gnavus-derived tryptamine and phenethylamine play a pathogenic role in gut dysbiosis-induced insulin resistance in type 2 diabetes (T2D) and IBS. We show levels of R. gnavus, tryptamine, and phenethylamine are positively associated with insulin resistance in T2D patients and IBS patients. Monoassociation of R. gnavus impairs insulin sensitivity and glucose control in germ-free mice. Mechanistically, treatment of R. gnavus-derived metabolites tryptamine and phenethylamine directly impair insulin signaling in major metabolic tissues of healthy mice and monkeys and this effect is mediated by the trace amine-associated receptor 1 (TAAR1)-extracellular signal-regulated kinase (ERK) signaling axis. Our findings suggest a causal role for tryptamine/phenethylamine-producers in the development of insulin resistance, provide molecular mechanisms for the increased prevalence of metabolic syndrome in IBS, and highlight the TAAR1 signaling axis as a potential therapeutic target for the management of metabolic syndrome induced by gut dysbiosis.
Topics: Humans; Animals; Mice; Insulin Resistance; Metabolic Syndrome; Irritable Bowel Syndrome; Diabetes Mellitus, Type 2; Gastrointestinal Microbiome; Dysbiosis; Phenethylamines; Tryptamines
PubMed: 37591886
DOI: 10.1038/s41467-023-40552-y -
Emergency Medicine Practice Nov 2023Management of patients who are acutely intoxicated with methamphetamine (a member of the substituted amphetamine class of drugs) can be resource-intensive for most... (Review)
Review
Management of patients who are acutely intoxicated with methamphetamine (a member of the substituted amphetamine class of drugs) can be resource-intensive for most emergency departments. Clinical presentations of the methamphetamine sympathomimetic toxidrome range from mild agitation to rhabdomyolysis, acute kidney injury, seizures, and intracranial hemorrhage. High-quality evidence on how to best manage these patients is lacking, and most research focuses on symptomatic interventions to control patients' agitation and hemodynamics. This review analyzes the best available evidence on the diagnosis and management of emergency department patients with substituted amphetamine toxicity and offers best-practice recommendations on treatment and disposition.
Topics: Humans; Methamphetamine; Emergency Service, Hospital; Amphetamine
PubMed: 37877728
DOI: No ID Found -
Expert Review of Clinical Pharmacology 2023The renewed interest in considering a range of stimulants, psychedelics and dissociatives as therapeutics emphasizes the need to draft an updated overview of these... (Review)
Review
INTRODUCTION
The renewed interest in considering a range of stimulants, psychedelics and dissociatives as therapeutics emphasizes the need to draft an updated overview of these drugs' clinical and pharmacological issues.
AREAS COVERED
The focus here was on: stimulants (e.g. amphetamines, methamphetamine, and pseudoephedrine; phenethylamines; synthetic cathinones; benzofurans; piperazines; aminoindanes; aminorex derivatives; phenmetrazine derivatives; phenidates); classical (e.g. ergolines; tryptamines; psychedelic phenethylamines), and atypical (e.g. PCP/ketamine-like dissociatives) psychedelics.Stimulant and psychedelics are associated with: a) increased central DA levels (psychedelic phenethylamines, synthetic cathinones and stimulants); b) 5-HT receptor subtypes' activation (psychedelic phenethylamines; recent tryptamine and lysergamide derivatives); and c) antagonist activity at NMDA receptors, (phencyclidine-like dissociatives).
EXPERT OPINION
Clinicians should be regularly informed about the range of NPS and their medical, psychobiological and psychopathological risks both in the acute and long term. Future research should focus on an integrative model in which pro-drug websites' analyses are combined with advanced research approaches, including computational chemistry studies so that in vitro and in vivo preclinical studies of index novel psychoactives can be organized. The future of psychedelic research should focus on identifying robust study designs to convincingly assess the potential therapeutic benefits of psychedelics, molecules likely to present with limited dependence liability levels.
Topics: Humans; Hallucinogens; Psychotropic Drugs; Central Nervous System Stimulants; Phenethylamines; Methamphetamine
PubMed: 37968919
DOI: 10.1080/17512433.2023.2279192 -
Pharmacology & Therapeutics Aug 2023Cannabis, cocaine, 3,4-methylenedioxymethamphetamine, and lysergic acid diethylamide are psychoactive substances with a significant increase in consumption during the... (Review)
Review
Cannabis, cocaine, 3,4-methylenedioxymethamphetamine, and lysergic acid diethylamide are psychoactive substances with a significant increase in consumption during the 21st century due to their popularity in medicinal and recreational use. New psychoactive substances (NPSs) mimic established psychoactive substances. NPSs are known as being natural and safe to consumers; however, they are neither natural nor safe, causing severe adverse reactions, including seizures, nephrotoxicity, and sometimes death. Synthetic cannabinoids, synthetic cathinones, phenethylamines, and piperazines are all examples of NPSs. As of January 2020, nearly 1000 NPSs have become documented. Due to their low cost, ease of availability, and difficulty of detection, misuse of NPSs has become a familiar and growing problem, especially in adolescents and young adults in the past decade. The use of NPSs is associated with higher risks of unplanned sexual intercourse and pregnancy. As many as 4 in 100 women seeking treatment for substance abuse are pregnant or nursing. Animal studies and human clinical case reports have shown that exposure to certain NPSs during lactation periods has toxic effects on neonates, increasing various risks, including brain damage. Nevertheless, neonatal toxicity effects of NPSs are usually unrecognized and overlooked by healthcare professionals. In this review article, we introduce and discuss the potential neonatal toxicity of NPSs, emphasizing synthetic cannabinoids. Utilizing the established prediction models, we identify synthetic cannabinoids and their highly accumulative metabolites in breast milk.
Topics: Humans; Infant, Newborn; Pregnancy; Cannabinoids; Phenethylamines; Psychotropic Drugs; Substance-Related Disorders; Prenatal Exposure Delayed Effects; Female; Animals; Disease Models, Animal; Maternal-Fetal Exchange
PubMed: 37290575
DOI: 10.1016/j.pharmthera.2023.108468 -
Current Organic Synthesis 2024In recent years, a growing global concern has been obesity. Patients with obesity are at major risk for developing a number of diseases. These diseases may significantly... (Review)
Review
In recent years, a growing global concern has been obesity. Patients with obesity are at major risk for developing a number of diseases. These diseases may significantly impact patient's daily lives and increase the mortality rate. Over a year, medication for obesity has undergone substantial changes. An amphetamine-like prescription drug called Phentermine (Adipex-P, Lomaira) is used to suppress appetite. In the last few years, Phentermine and its derivatives have attracted much attention due to their use in weight reduction; by reducing appetite or prolonging the feeling of fullness, it can aid in weight reduction. So, reviewing the synthesis of Phentermine and its derivatives becomes imperative. Therefore, various synthetic routes for Phentermine (from benzaldehyde, isopropyl phenyl ketone, dimethyl benzyl carbinol) and its derivatives synthesis, involving ortho-palladation, are also reviewed here comprehensively.
Topics: Phentermine; Humans; Appetite Depressants
PubMed: 37259208
DOI: 10.2174/1570179420666230530095245 -
Molecules (Basel, Switzerland) Jan 2023A concise review covering updated presence and role of 2-phenethylamines in medicinal chemistry is presented. Open-chain, flexible alicyclic amine derivatives of this... (Review)
Review
A concise review covering updated presence and role of 2-phenethylamines in medicinal chemistry is presented. Open-chain, flexible alicyclic amine derivatives of this motif are enumerated in key therapeutic targets, listing medicinal chemistry hits and appealing screening compounds. Latest reports in discovering new bioactive 2-phenethylamines by research groups are covered too.
Topics: Chemistry, Pharmaceutical; Receptors, G-Protein-Coupled; Phenethylamines; Receptors, Dopamine D2
PubMed: 36677913
DOI: 10.3390/molecules28020855