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Stimulants and psychedelics
Published in Ilana B. Crome, Richard Williams, Roger Bloor, Xenofon Sgouros, Substance Misuse and Young People, 2019
Substituted amphetamines are a diverse group of substances that have amphetamine as their parent compound and are often used recreationally. Cathinone, methcathinone, 3,4-methylenedioxy-methamphetamine (MDMA), and methamphetamine are examples. Methamphetamine (N-methyl-α-methylphenethylamine), and its two enantiomers, dextro-methamphetamine and levo-methamphetamine, are neurotoxic and highly addictive. They directly damage both dopamine and serotonin neurons in the CNS and can result in reduction in grey matter volume in several regions of the brain (Krasnova and Cadet, 2009; Yu et al., 2015). Methamphetamine neurotoxicity is also associated with increased risk of Parkinson’s disease (Thrash et al., 2009), and post-acute withdrawal symptoms, which persist for months (Cruickshank and Dyer, 2009). Methamphetamine is presented on the illicit market in two main forms: methamphetamine tablets and crystalline methamphetamine (‘crystal meth’, ‘ice’, ‘shabu’). Methamphetamine tablets, commonly known as ‘yaba’ in East and South-East Asia, are typically of low purity and often contain a large portion of caffeine, plus a range of other adulterants. Crystal meth is usually of much higher purity and it can be smoked, nasally insufflated or injected.
Interaction of Drugs of Dependence With Receptors
Published in S.J. Mulé, Henry Brill, Chemical and Biological Aspects of Drug Dependence, 2019
Dimethyl-, diethyl-, α-methyl-, a-ethyl-tryptamine, harmine, psilocybin, and ibogaine are included in this group of hallucinogenic amines. Freedman et al.91 showed that the indoleamine psychotomimetics exert LSD-like effects on 5-HT which differ from those of the phenyle thy lamines, e.g., mescaline and amphetamine. The indole-amines increase central 5-HT and at higher doses also increase 5-HIAA, a metabolite of 5-HT. Meek and Fuxe73 reported that after nialimide, dimethyl- and α-methyltryptamine reduce 5-HT accumulation. LSD and psilocybin are then without psychotomimetic effect. They suggested that the tryptamine derivatives may directly stimulate central 5-HT receptors, e.g., those involved in the hind limb extensor reflex. This action is shared by some substituted amphetamines. Therefore, a gradation of activity with respect to 5-HT receptors is shown by indole-amines, LSD producing a blockade of the physiological receptors, while DMT and a-MT produce stimulation.
Detection and Identification of Amphetamine and Related Stimulants
Published in John Caldwell, S. Joseph Mulé, Amphetamines and Related Stimulants: Chemical, Biological, Clinical, and Sociological Aspects, 2019
Using this information, the analyst can expect urine samples to contain higher drug levels than blood samples, for most of the amphetamines. However, for substituted amphetamines, such as benzphetamine, much lower levels of unchanged drug would be expected in urine. Also, the urinary pH has obvious significance, and an alkaline urine may indicate an attempt to prolong the drug’s effect and supress its appearance in urine.
Current and emerging drug therapies for the treatment of depression in adults with epilepsy
Published in Expert Opinion on Pharmacotherapy, 2019
Fenfluramine is a substituted amphetamine, acting primarily as a serotonin releasing agent with less effect on the release of noradrenaline and dopamine, which are primarily mediated by its metabolite Norfenfluramine. It was first approved in the US in the 1970s and later marketed for obesity [34]. It was withdrawn in 1997 after reports of cardiac effects (valve disease and fibrosis) and pulmonary hypertension [35]. The use of Fenfluramine in epilepsy was first reported in the 1980s. More recently, Fenfluramine has been investigated in Dravet syndrome showing a significant reduction in focal motor seizures [36]. Fenfluramine is currently under Phase III development by Zogenix (ZX008). Three double-blind, randomized, placebo-controlled studies for the adjunctive treatment in Dravet syndrome are being conducted and a long-term, open-label extension is planned [37]. The mechanism of action suggests an antidepressant effect but evidence is not available. The safety profile suggests potential limitations in terms of long-term tolerability but this is under review.
Takotsubo cardiomyopathy as a consequence of 4-fluoroamphetamine Mono-intoxication documented by toxicological analyses
Published in Clinical Toxicology, 2021
Sanaa M. Aly, Sylvie Deheul, Etienne Puymirat, Camille Richeval, Delphine Allorge, Jean-michel Gaulier
4-Fluoroamphetamine (4-FA), known as “ecstasy light”, is a widely used ring-substituted amphetamine. Three cases of severe adverse effects related to 4-FA use comprising Takotsubo’s syndrome (TTS) inverted type had been reported [1,2]. TTS is a rare specific cardiomyopathy which (about 1/36,000 in general population) appears to be increased in case of stimulant drug (e.g., amphetamine/methamphetamine) consumption. It is noteworthy that, in these cases, substances other than 4-FA were concomitantly used, and 4-FA use was analytically confirmed in only one case [1] for which it was suggested that the medication used during medical care might have contributed to trigger TTS [3].