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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 -
New designer phenethylamines 2C-C and 2C-P have abuse potential and induce neurotoxicity in rodents.Archives of Toxicology Apr 20212C (2C-x) is the general name for the family of phenethylamines containing two methoxy groups at the 2 and 5 positions of the benzene ring. The abuse of 2C family drugs... (Comparative Study)
Comparative Study
2C (2C-x) is the general name for the family of phenethylamines containing two methoxy groups at the 2 and 5 positions of the benzene ring. The abuse of 2C family drugs has grown rapidly, although the abuse potential and neurotoxic properties of 2C drugs have not yet been fully investigated. In this study, we investigated the abuse potential and neurotoxicity of 4-chloro-2,5-dimethoxyphenethylamine (2C-C) and 2,5-dimethoxy-4-propylphenethylamine (2C-P). We found that 2C-C and 2C-P produced conditioned place preference in a dose-dependent manner in mice, and increased self-administration in rats, suggesting that 2C-C and 2C-P have abuse potential. To investigate the neurotoxicity of 2C-C and 2C-P, we examined motor performance and memory impairment after high doses of 2C-C and 2C-P. High doses of 2C-C and 2C-P decreased locomotor activity, rota-rod performance, and lower Y-maze test, novel objective recognition test, and passive avoidance test scores. We also observed that 2C-C and 2C-P affected expression levels of the D1 dopamine receptor, D2 dopamine receptor, dopamine transporter, and phospho-dopamine transporter in the nucleus accumbens and the medial prefrontal cortex, and increased c-Fos immuno-positive cells in the nucleus accumbens. Moreover, high doses of 2C-C and 2C-P induced microglial activation, which is involved in the inflammatory reaction in the striatum. These results suggest that 2C-C and 2C-P have abuse potential by affecting dopaminergic signaling and induce neurotoxicity via initiating neuroinflammation at high doses.
Topics: Animals; Designer Drugs; Dopamine; Dose-Response Relationship, Drug; Inflammation; Locomotion; Male; Mice; Mice, Inbred C57BL; Neurotoxicity Syndromes; Nucleus Accumbens; Phenethylamines; Prefrontal Cortex; Rats; Rats, Sprague-Dawley
PubMed: 33515270
DOI: 10.1007/s00204-021-02980-x -
Medicine, Science, and the Law Apr 2021The term 'amphetamine' refers to a class of synthetic drugs which includes methamphetamine. The latter is a globally popular drug of abuse which induces euphoria,... (Review)
Review
The term 'amphetamine' refers to a class of synthetic drugs which includes methamphetamine. The latter is a globally popular drug of abuse which induces euphoria, affecting cognitive/psychomotor performance and sleep. It also provokes risk taking and violent behaviour. The central effects of methamphetamine are due to the overproduction of neurotransmitters, resulting in high levels of dopamine. In recent years, there have been significant increases in cases of methamphetamine abuse in North and South America, Australia and Asia due to its ready availability and low cost. The following review examines changing trends in methamphetamine use and problems that arise diagnostically in medico-legal cases in determining the significance of post-mortem blood levels, the relationship of these to ante-mortem levels, the possible effects on physical and psychological behaviours and the possible contribution of the drug to a lethal episode.
Topics: Amphetamine-Related Disorders; Autopsy; Blood Chemical Analysis; Diagnosis; Female; Forensic Toxicology; Humans; Internationality; Male; Methamphetamine
PubMed: 33423599
DOI: 10.1177/0025802420986707 -
Brain Research May 2020Mephedrone and MDMA are both constituents of party drugs, with mephedrone being relatively new compared to MDMA. This review compares current knowledge regarding the... (Comparative Study)
Comparative Study Review
Mephedrone and MDMA are both constituents of party drugs, with mephedrone being relatively new compared to MDMA. This review compares current knowledge regarding the patterns of usage and neuropsychobiological effects of both mephedrone and MDMA. Both drugs share common psychoactive effects, the duration of which is significantly shorter with mephedrone use, attributing towards a pattern of binge use among users. Both drugs have also been associated with adverse health, psychiatric, and neurocognitive problems. Whilst there is extensive research into the psychobiological problems induced by MDMA, the evidence for mephedrone is comparatively limited. The adverse effect profile of mephedrone appears to be less severe than that of MDMA. Users often believe it to be safer, although both drugs have been associated with overdoses. The neurotoxic potential of mephedrone appears to be low, whereas MDMA can cause long-term damage to the serotonergic system, although this needs further investigation. The abuse liability of mephedrone is significantly greater than that of MDMA, raising concerns regarding the impact of lifetime usage on users. Given that mephedrone is relatively new, the effects of long-term exposure are yet to be documented. Future research focused on lifetime users may highlight more severe neuropsychobiological effects from the drug.
Topics: Brain; Humans; Methamphetamine; N-Methyl-3,4-methylenedioxyamphetamine; Neurotoxicity Syndromes
PubMed: 32087112
DOI: 10.1016/j.brainres.2020.146740 -
Forensic Science International Sep 2022Suicide remains a global public health concern and the increased supply and use of synthetic stimulants globally may have implications for the burden of suicides... (Review)
Review
Suicide remains a global public health concern and the increased supply and use of synthetic stimulants globally may have implications for the burden of suicides attributable to substance use. This systematic review investigated any potential associations of stimulant use detected in post-mortem biological specimens and suicides. We conducted a systematic review and narrative synthesis (CRD42021237966). Medline, EMBASE, TOXLINE, and Scopus databases were searched for terms related to forensic toxicology, post-mortem toxicology, suicide and stimulants. The primary outcome was to estimate the prevalence of stimulant use in suicides. There were 26 studies whichcontributed to prevalence measures; in studies reporting at the individual compound level, suicides involved cocaine (0.1-23%), caffeine (3.2-22%), 3,4-methylenedioxymethamphetamine (0.1-17%), amphetamine (0.2-9.3%), methamphetamine (3.1-7%), and phentermine (0.9-1%). Overall, stimulant use in suicides was over-represented compared to estimates of stimulant use in the general population and has increased over time. Thirteen case reports used to contextualise suicides involving stimulants found no examples of cocaine or methamphetamine mono-intoxication of suicidal intent. This suggests mechanisms other than acute toxicity involved in stimulant-associated suicide. Future research by in-depth psychological autopsies of suicides involving stimulants, in combination with segmental hair analysis to determine the chronicity of stimulant exposure, may contribute to a better understanding of the burden of suicide attributable to stimulant use.
Topics: Amphetamine; Central Nervous System Stimulants; Cocaine; Humans; Methamphetamine; Suicide
PubMed: 35908335
DOI: 10.1016/j.forsciint.2022.111391 -
The Alkaloids. Chemistry and Biology 2020The Amaryllidaceae alkaloids are a distinctive chemotaxonomic feature of the subfamily Amaryllidoideae of the family Amaryllidaceae, which consists of 59 genera and >800... (Review)
Review
The Amaryllidaceae alkaloids are a distinctive chemotaxonomic feature of the subfamily Amaryllidoideae of the family Amaryllidaceae, which consists of 59 genera and >800 species distributed primarily in tropical and subtropical areas. Since the first isolation, ca. 140 ago, >600 structurally diverse Amaryllidaceae alkaloids have been reported from ca. 350 species (44% of all species in the subfamily). A few have been found in other plant families, but the majority are unique to the Amaryllidoideae. These alkaloids have attracted considerable research interest due to their wide range of biological and pharmacological activities, which have been extensively reviewed. In this chapter we provide a review of the 636 structures of isolated or tentatively identified alkaloids from plants of the Amaryllidoideae and their classification into 42 skeleton types, as well as a discussion on their distribution, and chemotaxonomical and chemoecological aspects.
Topics: Amaryllidaceae; Amaryllidaceae Alkaloids; Molecular Structure
PubMed: 32098649
DOI: 10.1016/bs.alkal.2019.10.002 -
Emergencias : Revista de La Sociedad...
Topics: Amphetamine; Emergency Service, Hospital; Hospitals; Humans; Laboratories; Methamphetamine
PubMed: 32692020
DOI: No ID Found -
Experimental Neurology Jun 2023Amphetamines, such as amphetamine (AMPH), methamphetamine (METH) and 3,4-methylenedioxymethamphetamine (MDMA), are the psychotropic substances widely abused in the... (Review)
Review
Amphetamines, such as amphetamine (AMPH), methamphetamine (METH) and 3,4-methylenedioxymethamphetamine (MDMA), are the psychotropic substances widely abused in the world. Amphetamines abuse can damage dopaminergic and serotonin neurons and cause neuroinflammation and neurotoxicity. Neuropsychiatric disorders induced by amphetamines abuse include depression, anxiety, auditory hallucinations, mania, and cognitive disorders, of which depression has a higher incidence. Transient receptor potential (TRP) channels can regulate the inflow and outflow of Ca. In TRP family, transient receptor potential canonical (TRPC) channels are closely associated with the development of some neurological diseases, such as Parkinson's disease and Alzheimer's disease. However, the correlation between TRPC channels and depression and the specific mechanism of TRPC channels in depression still haven't been fully clarified. This review elaborates the pathophysiological mechanisms of depression induced by amphetamines abuse, the functions of TRPC channels in the nervous system, and the possible correlation between TRPC channels and depression induced by amphetamines abuse, which would provide the theoretical basis for the development of the novel and effective therapeutic drugs for amphetamines abuse-induced depression.
Topics: Transient Receptor Potential Channels; Depression; Amphetamines; Methamphetamine; Central Nervous System Stimulants; Amphetamine
PubMed: 36996966
DOI: 10.1016/j.expneurol.2023.114391 -
Der Ophthalmologe : Zeitschrift Der... May 2021Approximately 40% of all open-angle glaucomas do not show high intraocular pressure (IOP). Vascular risk factors play an important role in the pathogeneses of normal... (Review)
Review
BACKGROUND
Approximately 40% of all open-angle glaucomas do not show high intraocular pressure (IOP). Vascular risk factors play an important role in the pathogeneses of normal pressure glaucoma but high pressure glaucoma is also often accompanied by significant vascular components.
OBJECTIVE
What are the practice relevant possibilities of vascular glaucoma treatment?
MATERIAL AND METHODS
An evaluation of scientific articles from PubMed dealing with vascular glaucoma was carried out.
RESULTS
The treatment of vascular risk factors in glaucoma patients requires a thorough medical history regarding vascular symptoms (peripheral vasospasm, tinnitus, migraine etc.) and information on the presence of systemic diseases. Furthermore, a 24h blood pressure profile and the determination of the fat metabolism status represent important and simple examinations.
CONCLUSION
Besides optimizing systemic blood pressure, reducing an increased central retinal venous pressure, treatment with statins, calcium channel blockers, Ginkgo biloba extract, increased physical exercise and fluid replacement are options to ameliorate vascular conditions. An interdisciplinary cooperation with general practitioners and internists is an important component of holistic treatment.
Topics: Ethanolamines; Glaucoma; Humans; Intraocular Pressure; Phenethylamines
PubMed: 33026527
DOI: 10.1007/s00347-020-01239-7 -
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