3-fluoromethcathinone and 4-fluoromethcathinone

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

Synthetic cathinone derivatives are commonly considered quasi-legal alternatives for stimulant drugs, such as cocaine and methamphetamine, but some derivatives are increasingly being detected in club drug formulations of Ecstasy or 'Molly' as substitutes for methylenedioxymethamphetamine (±-MDMA). Although several studies have evaluated the psychostimulant-like effects of synthetic cathinones, few cathinone compounds have been assessed for MDMA-like activity. In order to determine their likelihood of interchangeability with entactogenic club drugs, the discriminative stimulus effects of methcathinone, 4-fluoromethcathinone, 4-methylmethcathinone, 4-methylethcathinone, 3-fluoromethcathinone, pentedrone, and ethylone were assessed in Sprague-Dawley rats trained to discriminate 1.5 mg/kg racemic methylenedioxymethamphetamine (±-MDMA) from vehicle. Methamphetamine and the cathinones 4-fluoromethcathinone, 4-methylmethcathinone, 4-methylethcathinone, 3-fluoromethcathinone, pentedrone, and ethylone fully substituted for the discriminative stimulus effects of ±-MDMA. In contrast, methcathinone produced a maximum of only 43% ±-MDMA-appropriate responding and higher doses suppressed responding. Most, but not all of the cathinone compounds tested have discriminative stimulus effects similar to those of MDMA as well as psychostimulant-like effects; however, the potency of MDMA versus psychostimulant substitution varies substantially among the compounds, suggesting that a subset of synthetic cathinones are more MDMA-like than psychostimulant-like. These findings further highlight the highly-variable pharmacology of this class of compounds and suggest that those cathinones with MDMA-like effects may also have increased use as club drugs.

Topics: Acetone; Amphetamines; Animals; Discrimination Learning; Ethylamines; Male; Methamphetamine; Methylamines; N-Methyl-3,4-methylenedioxyamphetamine; Pentanones; Propiophenones; Rats