piperidines and cathinone

New psychoactive substances (NPS) pose a challenge for forensic and clinical toxicologists, as well as for legislators. We present our findings from cases where NPS have been detected in biological material. During the three-year period 2012-2014 we found NPS in 112 cases (out of 1058 analyzed), with 75 cases in 2014 alone. The prevalence of all NPS (15.1-17.6%) was similar to amphetamine alone that was detected in 15.1-16.5% of cases. The new drugs found belonged to the following classes: cathinones (88%), synthetic cannabinoids (5%), phenethylamines (3%), piperazines and piperidines (3%), arylalkylamines (1%) and other (1%). The drugs detected were (in the order of decreased frequency): 3-MMC (50), α-pyrrolidinopentiophenone (α-PVP) (23), pentedrone (16), 3',4'-methylenedioxy-α-pyrrolidinobutyrophenone (MDPBP) (12), synthetic cannabinoid UR-144 (7), ethcathinone (5), mephedrone (5), methylenedioxypyrovalerone (MDPV) (4), 4-methylethcathinone (4-MEC) (3), buphedrone (3), desoxypipradrol (2-DPMP) (3), methylone (2) and 2C-B (2). In single cases, 2-methylmethcathinone (2-MMC), 2C-P, eutylone, 25I-NBOMe, meta-chlorophenylpiperazine (mCPP), ephedrone, methiopropamine (MPA), and 5-(2-aminopropyl)benzofuran (5-APB) were found. One NPS was the sole agent in 35% of all cases, and two or more NPS were present in 19% of cases. NPS (one or more) with other conventional drugs (like amphetamines, cannabinoids, cocaine, and benzodiazepines) were detected in most (65%) of the cases. NPS were very often detected in the blood of drivers which was a challenge for toxicologists due to a lack of data on their influence on psychomotor performance. A review of concentrations showed a wide range of values in different types of cases, especially driving under the influence of drugs (DUID) and intoxication.

Topics: Alkaloids; Cannabinoids; Designer Drugs; Humans; Phenethylamines; Piperazines; Piperidines; Poland; Psychotropic Drugs; Substance Abuse Detection

A woman in her thirties was found dead on a bed. Considerable amounts of "aroma liquid" and "bath salt" products and hypnotic drug tablets were scattered beside the bed. Autopsy showed pulmonary congestion and edema. Gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS) analyses of "aroma liquid" and "bath salt" products showed the presence of new cathinone designer drugs, 4-methoxy PV8 (4-methoxy PHPP), PV9 (α-POP), and 4-methoxy PV9 (4-methoxy α-POP), and a dissociative agent, diphenidine. Drug screening in stomach contents, blood and hydrolyzed urine of the woman by GC-MS and liquid chromatography-tandem mass spectrometry (LC-MS/MS) revealed the presence of the above 4 types of drugs and 3 types of benzodiazepines, triazolam, flunitrazepam, and nitrazepam, and their metabolites. The above 7 drugs and 3 benzodiazepine metabolites were simultaneously determined by LC-MS/MS after modified QuEChERS (Quick, Easy, Cheap, Effective, Rugged, Safe) extraction using diazepam-d5 as the internal standard. The concentrations of 4-methoxy PV8, PV9, 4-methoxy PV9, and diphenidine in the femoral blood were 2.69, 0.743, 0.261, and 1.38μg/ml, respectively, which were significantly higher than concentrations reported in previous cases. Alcohol concentration in the femoral blood was 1.52mg/ml. Based on the pathological and toxicological findings, the cause of death was determined to be 3 types of cathinone drugs, 4-methoxy PV8, PV9, and 4-methoxy PV9, and diphenidine poisoning under the influence of 3 benzodiazepines and alcohol.

Topics: Adult; Alkaloids; Benzodiazepines; Cause of Death; Designer Drugs; Female; Humans; Piperidines; Tandem Mass Spectrometry

In order to analyse further the discriminative stimulus properties of stimulant drugs, rats were trained to discriminate 2.0 mg/kg of dl-cathinone in a two-lever operant task. Dose-related generalization was seen to cathinone itself and to a wide range of stimulant drugs including d-amphetamine, cocaine, methylphenidate, pipradrol and cathine, i.e. (+)norpseudoephedrine. The high degree of specificity of the cathinone cue at the specific training dose studied was shown by the fact that the following nonstimulant drugs failed to generalize at all to cathinone, even in large doses--haloperidol, chlordiazepoxide, fenfluramine and fentanyl. The cathinone cue at 2.0 mg/kg was probably of central origin because phydroxyamphetamine (a polar congener of amphetamine) failed to generalize to cathinone at a dose nearly 50 times the ED50 for amphetamine generalization. Phenylethylamine (PEA; alpha-demethylamphetamine) and deuterated phenylethylamine (alpha, alpha, d2-PEA), a long acting derivative of phenylethylamine which is resistant to metabolism by monoamine oxidase, produced at most partial (60%) generalization to cathinone, even in large doses. alpha-Demethylcathinone failed to generalize at all to cathinone at doses up to 10 times the ED50 for cathinone. Thus, the alpha-methyl groups of both amphetamine and cathinone are important in determining their cue properties. The involvement of dopaminergic systems in the cathinone cue was investigated by examining generalization to apomorphine and antagonism by haloperidol. Apomorphine produced at most 29% generalization to cathinone. Haloperidol, at doses up to 0.3 mg/kg, produced at most 50% antagonism of both the cathinone cue and of the ability of amphetamine to substitute for cathinone. It is suggested that the evidence for dopaminergic mediation of the cue properties of cathinone and of other CNS stimulants is somewhat tenuous, whilst endogenous phenylethylamine may play some part in the mediation of the stimulant cue. Haloperidol, alone and in conjunction with amphetamine or cathinone, produced a remarkable tendency for subjects to emit a greater proportion of their total responses on the inoperative rather than the operative lever than was seen after saline or injections of vehicle. This action of a neuroleptic drug suggests, in accordance with Colpaert, Niemegeers and Janssen (1977), that in drug discrimination antagonism studies involving neuroleptics, and perhaps other drugs, quantal (lever selection) rathe

Topics: Alkaloids; Animals; Brain; Central Nervous System Stimulants; Cocaine; Conditioning, Operant; Cues; Dextroamphetamine; Discrimination Learning; Female; Generalization, Stimulus; Methylphenidate; Phenylpropanolamine; Piperidines; Rats

Rats were trained to discriminate between the stimulus properties of 0.6 mg/kg l-cathinone and its vehicle in a two-lever, food-motivated operant task. Once trained, rats showed a dose-dependent decrease in discrimination performance with lower l-cathinone doses and analysis of the dose-response relationship indicated an ED50 of 0.19 mg/kg. Administration of either dl-or d-cathinone produced a pattern of discriminative responding similar to l-cathinone with ED50s of 0.29 and 0.63 mg/kg, respectively. Thus, the potency of the racemeric cathinone lies approximately midway between that of the two isomers. Time-course data indicate that l-cathinone has a peak effect at 15-30 min post-administration with a duration of 180 min. Pretreatment with the serotonic receptor blocker pirenperone did not affect l-cathinone discrimination, whereas pretreatment with 0.2 mg/kg haloperidol, a dopamine receptor blocking agent, attenuated the l-cathinone discrimination. These data suggest that the stimulus properties of l-cathinone are possibly mediated by brain dopaminergic systems.

Topics: Alkaloids; Animals; Discrimination, Psychological; Dose-Response Relationship, Drug; Generalization, Psychological; Haloperidol; Male; Piperidines; Rats; Rats, Inbred Strains; Stereoisomerism; Time Factors