pentylone and cathinone

The synthetic cathinones are a class of designer drugs of abuse that share a common core scaffold. The pharmacokinetic profiles of the synthetic cathinones vary based on the substitutions to the core scaffold.. To provide a summary of the literature regarding the pharmacokinetic characteristics of the synthetic cathinones, with a focus on the impact of the structural modifications to the pharmacokinetics.. In many, but not all, instances the pharmacokinetic characteristics of the synthetic cathinones can be reasonably predicted based on the substitutions to the core scaffold. Mephedrone and methylone are chemically alike and have similar T. Continued research will lead to a better understanding of the pharmacokinetic changes associated with structural modifications to the cathinone scaffold, and potentially in the long range, enhanced overdose and addiction therapy. Additionally, the areas of polydrug use and pharmacogenetics have been largely overlooked with regard to synthetic cathinones.

Topics: Alkaloids; Amphetamines; Animals; Designer Drugs; Humans; Methamphetamine; Substance-Related Disorders; Synthetic Drugs

The production and consumption of new psychoactive substances (NPSs) has been raising a major concern worldwide. Due to easy access and available information, many NPSs continue to be synthesized with an alarming increase of those available to purchase, despite all the control efforts created. A new analytical method was developed and validated to determine a group of phenethylamines and synthetic cathinones: cathinone, flephedrone, buphedrone, 4-MTA, α-PVP, methylone, 2C-P, ethylone, pentylone, MDPV and bromo-dragonFLY in whole blood. A mixed-mode solid phase extraction was applied to 250 μL of sample, and the extracts were derivatized with fast microwave technique before being analyzed by gas chromatography-mass spectrometry (GC-MS). The validation procedure followed the Scientific Working Group for Forensic Toxicology (SWGTOX) guidelines with parameters that included selectivity, linearity, limits of detection and quantification, intra- and inter-day precision and accuracy, recoveries and stability. The method presented linearity between 5 and 500 ng/mL for cathinone, buphedrone, 4-MTA, methylone, 2C-P and bromo-dragonFLY, 10-500 ng/mL for flephedrone, ethylone, pentylone and MDPV, and 40-500 ng/mL for α-PVP, with determination coefficients above 0.99 for all analytes. Recoveries ranged between 70.3% and 116.6%, and regarding intra- and inter-day precision, the relative mean errors were typically lower than 8.6%. The method was successfully applied to over 100 authentic samples from the Laboratory of Chemistry and Forensic Toxicology, Centre Branch, of the National Institute of Legal Medicine and Forensic Sciences, Portugal.

Topics: Acetone; Alkaloids; Amphetamines; Designer Drugs; Ethylamines; Forensic Toxicology; Gas Chromatography-Mass Spectrometry; Humans; Limit of Detection; Methamphetamine; Microwaves; Pentanones; Phenethylamines; Psychotropic Drugs; Pyrrolidines; Substance Abuse Detection

Increasing reports of neurological and psychiatric complications due to psychostimulant synthetic cathinones (SCs) have recently raised public concern. However, the precise mechanism of SC toxicity is unclear. This paucity of understanding highlights the need to investigate the in-vitro toxicity and mechanistic pathways of three SCs: butylone, pentylone, and 3,4-Methylenedioxypyrovalerone (MDPV). Human neuronal cells of SH-SY5Y were cultured in supplemented DMEM/F12 media and differentiated to a neuronal phenotype using retinoic acid (10 μM) and 12-

Topics: Adenosine Triphosphate; Alkaloids; Amphetamines; Benzodioxoles; Calcium; Caspase 3; Caspase 7; Cell Death; Cell Line, Tumor; Dopaminergic Neurons; Energy Metabolism; Homeostasis; Humans; Mitochondria; Neurotoxins; Oxidative Stress; Oxygen Consumption; Pyrrolidines; Reactive Oxygen Species; Synthetic Cathinone

Synthetic cathinones continue to emerge in recreational drug markets worldwide. 1-(1,3-Benzodioxol-5-yl)-2-(methylamino)butan-1-one (butylone) and 1-(1,3-benzodioxol-5-yl)-2-(methylamino)pentan-1-one (pentylone) are derivatives of the cathinone compound, 1-(1,3-benzodioxol-5-yl)-2-(methylamino)propan-1-one (methylone), that are being detected in drug products and human casework.. The purpose of the present study was to examine the neuropharmacology of butylone and pentylone using in vitro and in vivo methods.. In vitro uptake and release assays were carried out in rat brain synaptosomes and in cells expressing human dopamine transporters (DAT) and 5-HT transporters (SERT). In vivo microdialysis was performed in the nucleus accumbens of conscious rats to assess drug-induced changes in neurochemistry.. Our data demonstrate that increasing the α-carbon chain length of methylone creates "hybrid" transporter compounds which act as DAT blockers but SERT substrates. Nevertheless, butylone and pentylone elevate extracellular dopamine and stimulate motor activity, suggesting both drugs possess significant risk for abuse.

Topics: 3,4-Methylenedioxyamphetamine; Alkaloids; Amphetamines; Animals; Central Nervous System Stimulants; Dopamine Antagonists; Dopamine Plasma Membrane Transport Proteins; Dose-Response Relationship, Drug; HEK293 Cells; Humans; Male; Methamphetamine; Nucleus Accumbens; Rats; Rats, Sprague-Dawley; Synaptosomes; Synthetic Drugs

Synthetic cathinones continue to be sold as "legal" alternatives to methamphetamine or cocaine. As these marginally legal compounds become controlled, suppliers move to other, unregulated compounds.. The purpose of these experiments was to determine whether several temporarily controlled cathinone compounds, which are currently abused on the street, stimulate motor activity and have discriminative stimulus effects similar to cocaine and/or methamphetamine.. Methcathinone, pentedrone, pentylone, 3-fluoromethcathinone (3-FMC), and 4-methylethcathinone (4-MEC) were tested for locomotor stimulant effects in mice and subsequently for substitution in rats trained to discriminate cocaine (10 mg/kg, i.p.) or methamphetamine (1 mg/kg, i.p.) from saline.. Methcathinone, pentedrone, and pentylone produced locomotor stimulant effects which lasted up to 6 h. In addition, pentylone produced convulsions and lethality at 100 mg/kg. 4-MEC produced locomotor stimulant effects which lasted up to 2 h. Methcathinone, pentedrone, pentylone, 3-FMC, and 4-MEC each produced discriminative stimulus effects similar to those of cocaine and methamphetamine.. All of the tested compounds produce discriminative stimulus effects similar to either those of cocaine, methamphetamine, or both, which suggests that these compounds are likely to have similar abuse liability to cocaine and/or methamphetamine. Pentylone may be more dangerous on the street, as it produced adverse effects at doses that produced maximal stimulant-like effects.

Topics: Alkaloids; Amphetamines; Animals; Central Nervous System Stimulants; Cocaine; Discrimination Learning; Dose-Response Relationship, Drug; Illicit Drugs; Male; Methamphetamine; Mice; Motor Activity; Rats; Rats, Sprague-Dawley