RESUMO
Synthetic cannabinoids are psychoactive substances designed to mimic the euphorigenic effects of the natural cannabis. Novel unregulated compounds appear once older compounds become illegal. It has been previously reported that synthetic cannabinoids are different than Δ9 -tetrahydrocannabinol (Δ9 -THC) as they have chemical structures unrelated to Δ9 -THC, different metabolism and, often, greater toxicity. This study aimed to investigate the effects of three novel synthetic cannabinoids and pure Δ9 -THC on body temperature, nociceptive threshold, anxiety, memory function, locomotor and exploratory parameters, and depression. We performed a battery of behavioural and motor tests starting 50 minutes post i.p. injection of each drug to adult ICR mice. The synthetic cannabinoids that were used are AB-FUBINACA, AB-CHMINACA and PB-22. All synthetic cannabinoids and Δ9 -THC caused hypothermia, but only Δ9 -THC induced a clear antinociceptive effect. All synthetic cannabinoids and Δ9 -THC caused decreased anxiety levels, spatial memory deficits and decreased exploratory behaviour as measured in the elevated plus maze, Y-maze and staircase paradigm, respectively. However, all synthetic cannabinoids but not Δ9 -THC demonstrated decreased locomotor activity in the staircase test. Moreover, only AB-FUBINACA and Δ9 -THC affected the gait balance and grip strength of the mice as was assessed by the latency time to fall from a rod. In the forced swimming test, PB-22 caused elevated depression-like behaviour while AB-FUBINACA induced a reversed effect. These results suggest varied effects among different synthetic cannabinoids and Δ9 -THC. Further studies are needed to characterize the overall effects and differences between these synthetic cannabinoids and Δ9 -THC.
Assuntos
Dronabinol/farmacologia , Indazóis/farmacologia , Psicotrópicos/farmacologia , Valina/análogos & derivados , Animais , Ansiedade/fisiopatologia , Temperatura Corporal/efeitos dos fármacos , Depressão/fisiopatologia , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Memória/efeitos dos fármacos , Camundongos Endogâmicos ICR , Atividade Motora/efeitos dos fármacos , Nociceptividade/efeitos dos fármacos , Limiar Sensorial/efeitos dos fármacos , Valina/farmacologiaRESUMO
2-Methiopropamine [1-(thiophen-2-yl)-2-methylaminopropane, 2-MPA], a thiophene analogue of methamphetamine, is available from online vendors selling "research chemicals." The first samples were seized by the German police in 2011. As it is a recreational stimulant, its inclusion in routine drug screening protocols should be required. The aims of this study were to identify the phase I and II metabolites of 2-MPA in rat and human urine and to identify the human cytochrome-P450 (CYP) isoenzymes involved in its phase I metabolism. In addition, the detectability of 2-MPA in urine samples using the authors' well-established gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-linear ion trap-mass spectrometry (LC-MS(n)) screening protocols was also evaluated. The metabolites were isolated from rat and human urine samples by solid-phase extraction without or following enzymatic cleavage of conjugates. The phase I metabolites, following acetylation, were separated and identified by GC-MS and/or liquid chromatography-high-resolution linear ion trap mass spectrometry (LC-HR-MS(n)) and the phase II metabolites by LC-HR-MS(n). The following major metabolic pathways were proposed: N-demethylation, hydroxylation at the side chain and at the thiophene ring, and combination of these transformations followed by glucuronidation and/or sulfation. CYP1A2, CYP2C19, CYP2D6, and CYP3A4 were identified as the major phase I metabolizing enzymes. They were also involved in the N-demethylation of the analogue methamphetamine and CYP2C19, CYP2D6, and CYP3A4 in its ring hydroxylation. Following the administration of a typical user's dose, 2-MPA and its metabolites were identified in rat urine using the authors' GC-MS and the LC-MS(n) screening approaches. Ingestion of 2-MPA could also be detected by both protocols in an authentic human urine sample.
Assuntos
Cromatografia Líquida/métodos , Cromatografia Gasosa-Espectrometria de Massas/métodos , Metanfetamina/urina , Tiofenos/urina , Animais , Sistema Enzimático do Citocromo P-450/metabolismo , Humanos , Masculino , Metanfetamina/análogos & derivados , Metanfetamina/metabolismo , Ratos , Ratos Wistar , Tiofenos/química , Tiofenos/metabolismoRESUMO
A study was conducted to assess the influence of a possible contamination of the victim's clothing by gunpowder residue on the estimation of shooting distance. The study was focused on the scenario in which the contamination might be caused by the surface on which the shot victim could fall. Contamination of two types of textile was examined after contact with two types of surfaces. One round was fired above those surfaces (the line of firing parallel to the surface) prior to the contact. It was found that few gunpowder residue particles could be transferred to the clothing. These findings should be taken into account when interpreting results for shooting distance estimation in cases when a minute quantity of gunpowder residue particles is found around the bullet entrance hole.