4-fluoromethcathinone and cathinone

Synthetic stimulants commonly sold as "bath salts" are an emerging abuse problem in the U.S. Users have shown paranoia, delusions, and self-injury. Previously published in vivo research has been limited to only two components of bath salts (mephedrone and methylone). The purpose of the present study was to evaluate in vivo effects of several synthetic cathinones found in bath salts and to compare them to those of cocaine (COC) and methamphetamine (METH). Acute effects of methylenedioxyphyrovalerone (MDPV), mephedrone, methylone, methedrone, 3-fluoromethcathinone (3-FMC), 4-fluoromethcathinone (4-FMC), COC, and METH were examined in male ICR mice on locomotor activity, rotorod, and a functional observational battery (FOB). All drugs increased locomotor activity, with different compounds showing different potencies and time courses in locomotor activity. 3-FMC and methylone decreased performance on the rotorod. The FOB showed that in addition to typical stimulant induced effects, some synthetic cathinones produced ataxia, convulsions, and increased exploration. These results suggest that individual synthetic cathinones differ in their profile of effects, and differ from known stimulants of abuse. Effects of 3-FMC, 4-FMC, and methedrone indicate these synthetic cathinones share major pharmacological properties with the ones that have been banned (mephedrone, MDPV, methylone), suggesting that they may be just as harmful.

Topics: Alkaloids; Analysis of Variance; Animals; Central Nervous System Stimulants; Cocaine; Dose-Response Relationship, Drug; Exploratory Behavior; Hypoglycins; Male; Methamphetamine; Mice; Mice, Inbred ICR; Motor Activity; Observation; Propiophenones; Psychomotor Performance; Rotarod Performance Test; Time Factors

Workplace drug testing in Australia is usually adherent to one of two standards, AS/NZS 4308:2008 for urine or AS 4760:2006 for oral fluid. These standards prescribe the drugs tested, devices used and testing methodology followed by the testing agency. However, they are not comprehensive and for many years workers have been able to consume novel psychoactive substances to avoid detection and without consequences. Here, we present a validated method for the detection of 32 Synthetic Stimulant and Hallucogenic drugs, commonly sold as bath salts, in oral fluid. These drugs are cathinone, ephedrone, methylone, flephedrone, MDA, PMA, methedrone, TMA, MDMA, butylone, mephedrone, MDEA, MEC, pentedrone, MBDB, MTA, Alpha-PVP, MPBP, 2C-B, MDPV, DOB, 2C-T-2, TFMPP, DOET, 2C-T-7, naphyrone, MDAI, FMA, DMA, 25C-NBOMe, 25B-NBOMe and 25T4-NBOMe. Sample preparation was undertaken using a simple protein precipitation in acetonitrile. Chromatographic separation was achieved in 7.5 min on a Kinetex F5 column (50 mm × 3 mm × 2.6 μm) using 0.1% formic acid in water and acetonitrile as the mobile phases. The method was validated with limit of detection (1 ng/mL), limit of quantitation (2.5 ng/mL), selectivity, linearity (2.5-500 ng/mL), accuracy (85.3-108.4% of the target concentration) and precision (1.9-14%). This method was applied to 12 samples previously submitted for routine testing and two were found to contain 2-CB and DOB (5 and 4 ng/mL) and, MPBP and TFMPP (both at 4 ng/mL). This method provides for the rapid detection of a large number of compounds in oral fluid which is readily applicable to routine testing laboratories.

Topics: Alkaloids; Anisoles; Australia; Benzylamines; Dimethoxyphenylethylamine; Humans; Illicit Drugs; Methamphetamine; Pentanones; Phenethylamines; Propiophenones; Psychotropic Drugs; Pyrrolidines; Saliva; Substance Abuse Detection

Flephedrone (4-fluoromethcathinone, 4-FMC) was analysed using (1)H, (13)C, (15)N HMBC, and (19)F observe spectroscopy, gas chromatography-flame ionisation detection (GC-FID), and electrospray ionisation-mass spectrometry (ESI-MS). Analysis of four 4-FMC samples (from a Bristol nightclub in 2013) showed that they all contained benzocaine as the cutting agent present in different amounts from 5 to 12%. Using these methods, we successfully differentiated between flephedrone regioisomers and mephedrone in an analytical method validated for flephedrone as a substituted cathinone. The data show that these now illegal cathinone-derived stimulants (highs) are now being cut; users cannot be certain of the purity of the drug they are taking. Furthermore, there are risks from the pharmaceutically active cutting agents themselves.

Topics: Alkaloids; Benzocaine; Gas Chromatography-Mass Spectrometry; Magnetic Resonance Spectroscopy; Methamphetamine; Propiophenones; Spectrometry, Mass, Electrospray Ionization

Flephedrone is an analogue of cathinone - chemically similar to ephedrine, cathine and other amphetamines. Conformations of all isomers of flephedrone have been studied at the quantum-chemical level. Calculations have been performed using DFT and MP2 methods with two basis sets - 6-31G and 6-31G(d,p). Results show that there are low energy conformers for the ortho, meta, and para isomers that are connected by way of low-barrier transition states. Boltzmann distribution of population predicts the highest population for the 1-meta conformer with a 10% increase in solution. The molecular electrostatic potential surface data for each molecule has been calculated revealing likely reaction sites.

Topics: Alkaloids; Amphetamines; Designer Drugs; Molecular Conformation; Propiophenones; Psychotropic Drugs; Static Electricity

The use of designer drugs commonly marketed as bath salts or plant food has risen dramatically in recent years. Several different synthetic cathinones have been indentified in these products, including mephedrone, 3,4-methylenedioxypyrovalerone (MDPV), and 4-fluoromethcathinone (flephedrone). We report a case of bath salt intoxication with quantitative MDPV and flephedrone levels in a patient's serum and urine, and from the bath salt product.. A 23-year-old male with a prior psychiatric history arrived via EMS for bizarre behavior, suicidality, and hallucinations after reportedly insufflating a bath salt. He was found to have MDPV levels of 186 and 136 ng/mL in his serum and urine, respectively, and flephedrone levels of 346 and 257 ng/mL in the serum and urine, respectively. The white powder in question was found to contain 143 μg MDPV and 142 μg flephedrone per milligram powder. His psychosis and agitation resolved with lorazepam, droperidol, and observation in the emergency department.. Agitation, psychosis, movement disorders, tachycardia, and hypertension have all been attributed to the use of MDPV; there are no prior reports detailing clinical experience with flephedrone. Considering that our patient's serum flephedrone levels were twofold higher than his MDPV level, it is likely flephedrone contributed to his clinical toxicity. This case suggests the possibility that fluorinated cathinones, such as flephedrone, may have altered metabolism and/or elimination which may affect their course of clinical toxicity. This case highlights the evolving composition of synthetic cathinones found in bath salt products.

Topics: Alkaloids; Benzodioxoles; Designer Drugs; Droperidol; Humans; Insufflation; Lorazepam; Male; Propiophenones; Psychoses, Substance-Induced; Psychotic Disorders; Psychotropic Drugs; Pyrrolidines; Salts; Synthetic Cathinone; Young Adult