mephedrone and pyrovalerone

Topics: Benzodioxoles; Central Nervous System Stimulants; Emergency Nursing; Humans; Illicit Drugs; Methamphetamine; Pyrrolidines; Substance-Related Disorders; Synthetic Cathinone

The term "synthetic cathinones" is fairly new, but, although the abuse of synthetic cathinones is a recent problem, research on cathinone analogs dates back >100 years. One structural element cathinone analogs have in common is an α-aminophenone moiety. Introduction of amine and/or aryl substituents affords a large number of agents. Today, >40 synthetic cathinones have been identified on the clandestine market and many have multiple "street names." Many cathinone analogs, although not referred to as such until the late 1970s, were initially prepared as intermediates in the synthesis of ephedrine analogs. The cathinones do not represent a pharmacologically or mechanistically homogeneous class of agents. Currently abused synthetic cathinones are derived from earlier agents and seem to produce their actions primarily via the dopamine, norepinephrine, and/or serotonin transporter; that is, they either release and/or inhibit the reuptake of one or more of these neurotransmitters. The actions of these agents can resemble those of central stimulants such as methamphetamine, cocaine, and/or empathogens such as 1-(3,4-methylenedioxyphenyl)-2-aminopropane (Ecstasy) and/or produce other effects. Side effects are primarily of a neurological and/or cardiovascular nature. The use of the "and/or" term is emphasized because synthetic cathinones represent a broad class of agents that produce a variety of actions; the agents cannot be viewed as being pharmacologically equivalent. Until valid structure-activity relationships are formulated for each behavioral/mechanistic action, individual synthetic cathinones remain to be evaluated on a case-by-case basis. Treatment of synthetic cathinone intoxication requires more "basic science" research. At this time, treatment is mostly palliative.

Topics: Alkaloids; Animals; Central Nervous System Stimulants; Drug Delivery Systems; Humans; Illicit Drugs; Methamphetamine; Pyrrolidines; Structure-Activity Relationship; Substance-Related Disorders

Since the classification of miaow miaow (mephedrone) as a class B drug in April this year, a new drug is emerging as a so-called 'legal high'. Deaths have already been attributed to ivory wave in different parts of the country.. A case study is presented, and relevant literature is explored in order to better understand the drug and its effects in the human body.. Overstimulation of the nervous system can cause acute paranoid psychosis, dizziness, hyperthermia and potential fitting. Effects on the cardiovascular system include tachycardia, chest pains, S-T segment changes, and blood pressure variations with potential renal implications.. Ivory wave's popularity seems to be growing and it seems quite plausible that this drug could become 'the next mephedrone'. Clinicians should be aware of its likely presentations, dangers, and management.

Topics: Benzodioxoles; Chest Pain; Drug Combinations; Humans; Illicit Drugs; Lidocaine; Methamphetamine; Pyrrolidines; United Kingdom

Synthetic cathinones are beta-ketone amphetamine analogs that have emerged as a heterogeneous class of abused compounds that function as either monoamine transporter substrates or inhibitors. Pre-clinical drug discrimination procedures are useful for interrogating structure-activity relationships of abuse-related drug effects; however, in vivo structure-activity relationship comparisons between synthetic cathinones with different mechanisms of action are lacking. The aim of the present study was to determine whether the cocaine-like discriminative stimulus effects of the monoamine transporter inhibitor alpha-pyrrolidinovalerophenone (alpha-PVP) and the monoamine transporter substrate methcathinone were differentially sensitive to 3,4-methylenedioxy and 4-methyl substitutions. Male rhesus monkeys (n = 4) were trained to discriminate intramuscular cocaine (0.32 mg/kg) from saline in a two-key food-reinforced discrimination procedure. Potency and timecourse of cocaine-like discriminative stimulus effects were determined for (±)-alpha-PVP, (±)-methcathinone and their 3,4-methylenedioxy or 4-methyl analogs. Alpha-PVP and methcathinone produced dose- and time-dependent cocaine-like effects. A 3,4-methylenedioxy addition to either alpha-PVP or methcathinone (methylone) did not alter the potency or efficacy to produce cocaine-like effects, but did prolong the time course. A 4-methyl addition to alpha-PVP (pyrovalerone) did not alter the potency or efficacy to produce cocaine-like effects, but did prolong the time course. In contrast, addition of a 4-methyl moiety to methcathinone (4MMC; mephedrone) significantly attenuated efficacy to produce cocaine-like effects. Overall, these results suggest different structural requirements for cocaine-like discriminative stimulus effects of monoamine transporter inhibitor and substrate synthetic cathinone analogs. Given that 4MMC is more hydrophobic than MDMC, these results suggest that hydrophobicity may be an important determinant for limiting monoamine transporter substrate abuse-related behavioral effects.

Topics: Animals; Central Nervous System Stimulants; Cocaine; Conditioning, Operant; Discrimination Learning; Dopamine Uptake Inhibitors; Injections, Intramuscular; Macaca mulatta; Male; Methamphetamine; Propiophenones; Pyrrolidines; Reinforcement, Psychology

Topics: Administration, Inhalation; Adult; Alkaloids; Catha; Central Nervous System Stimulants; Diagnosis, Differential; Emergency Service, Hospital; Female; Humans; Mental Status Schedule; Methamphetamine; Psychoses, Substance-Induced; Pyrrolidines; Serotonin; Serotonin Syndrome