Pharmacological characterization of designer cathinones in vitro
Linda D. Simmler,T. A. Buser,Massimiliano Donzelli,York Schramm,L. H. Dieu,Jörg Huwyler,Sylvie Chaboz,Marius C. Hoener,Matthias E. Liechti +8 more
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Designer β‐keto amphetamines (e.g. cathinones, ‘bath salts’ and ‘research chemicals’) have become popular recreational drugs, but their pharmacology is poorly characterized.Abstract:
Background and purpose: Designer beta-keto amphetamines (e.g., cathinones, "bath salts," and "research chemicals") have become popular recreational drugs, but their pharmacology is poorly characterized. Experimental approach: We determined the potencies of cathinones to inhibit dopamine (DA), noradrenaline (NA), and serotonin (5-hydroxytryptamine [5-HT]) transport into transporter-transfected human embryonic kidney 293 cells, DA and 5-HT efflux from monoamine-preloaded cells, and monoamine receptor binding affinity. Key results: Mephedrone, methylone, ethylone, butylone, and naphyrone act as nonselective monoamine uptake inhibitors, similar to cocaine. Mephedrone, methylone, ethylone, and butylone also release 5-HT, similar to 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) and other entactogens. Cathinone, methcathinone, and flephedrone act as preferential DA and NA uptake inhibitors and DA releasers, similar to amphetamine and methamphetamine. Pyrovalerone and 3,4-methylenedioxypyrovalerone (MDPV) are highly potent and selective DA and NA transporter inhibitors but unlike amphetamines do not release monoamines. The non-beta-keto amphetamines are trace amine-associated receptor 1 ligands, whereas cathinones are not. All cathinones showed high blood-brain barrier permeability in an in vitro model. Mephedrone and MDPV exhibited particularly high permeability. Conclusions and implications: Cathinones have considerable pharmacological differences that form the basis for their suggested classification into three groups. The predominant action of all cathinones on the DA transporter is likely associated with a considerable risk of addiction. (c) 2012 The Authors. British Journal of Pharmacology (c) 2012 The British Pharmacological Society.read more
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Khat and synthetic cathinones: a review
Maria João Valente,Paula Guedes de Pinho,Maria de Lourdes Bastos,Félix Carvalho,Márcia Carvalho,Márcia Carvalho +5 more
TL;DR: The present work provides a review on khat and synthetic cathinones, concerning their historical background, prevalence, patterns of use, legal status, chemistry, pharmacokinetics, pharmacodynamics, and their physiological and toxicological effects on animals and humans.
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Synthetic Cathinones: A New Public Health Problem
TL;DR: The major clinical effects of synthetic cathinones are reviewed to highlight their impact on public health.
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Substituted methcathinones differ in transporter and receptor interactions.
Amy J. Eshleman,Katherine M. Wolfrum,Meagan G. Hatfield,Robert A. Johnson,Kevin V. Murphy,Kevin V. Murphy,Aaron Janowsky +6 more
TL;DR: This is the first report on aspects of substituted methcathinone efficacies at serotonin (5-HT) receptors and in superfusion release assays, and indicates direct interactions with hVMAT2 and serotonin, dopamine, and hSigma1 receptors may not explain psychoactive effects.
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Receptor interaction profiles of novel psychoactive tryptamines compared with classic hallucinogens
TL;DR: The receptor interaction profiles of the tryptamines predict hallucinogenic effects that are similar to classic serotonergic hallucinogens but also MDMA-like psychoactive properties.
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Psychoactive “bath salts”: Not so soothing
TL;DR: More research on the pharmacology and toxicology of abused cathinones is needed to inform public health policy and develop strategies for treating medical consequence of bath salts abuse.
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