RESUMO
The new psychoactive substances (NPS) in Colombia are detected by national authorities, in blotters strip, in different circumstances and places: airports, music concerts, discos and parks. Blotters are marketed as LSD and cause several cases of intoxication and death in some consumers: due to acute intoxication or when mixed with other drugs and may have different effects on the central nervous system (CNS). This study was conducted to research into and identify the chemical composition of the drugs impregnated in the blotters sold in two Colombian cities. This research provides the analysis of 70 doses coming from forensic cases of the Colombian Attorney General's Office in Bogota and from the Laboratory of Narcotics of the Colombian National Institute of Legal Medicine and Forensic Sciences (North Headquarter) in Barranquilla. Mixtures of drugs, such as DOB, 25I-NBOMe, MDMA and 25I-NBOMe imine were found within the blotters through gas chromatography coupled to mass spectrometry (CGMS); these drugs are classified by international authorities as NPS belonging to the phenylethylamines group. The results clearly warn about a growing public health problem in the country.
Assuntos
2,5-Dimetoxi-4-Metilanfetamina/análogos & derivados , Dimetoxifeniletilamina/análogos & derivados , Tráfico de Drogas , Drogas Ilícitas/isolamento & purificação , N-Metil-3,4-Metilenodioxianfetamina/isolamento & purificação , 2,5-Dimetoxi-4-Metilanfetamina/isolamento & purificação , Administração Sublingual , Colômbia , Drogas Desenhadas/isolamento & purificação , Dimetoxifeniletilamina/isolamento & purificação , Contaminação de Medicamentos , Humanos , Papel , Transtornos Relacionados ao Uso de SubstânciasRESUMO
2,5-Dimethoxy-4-substituted phenylisopropylamines and phenethylamines are 5-hydroxytryptamine (serotonin) (5-HT)(2A/2C) agonists. The former are partial to full agonists, whereas the latter are partial to weak agonists. However, most data come from studies analyzing phospholipase C (PLC)-mediated responses, although additional effectors [e.g., phospholipase A(2) (PLA(2))] are associated with these receptors. We compared two homologous series of phenylisopropylamines and phenethylamines measuring both PLA(2) and PLC responses in Chinese hamster ovary-K1 cells expressing human 5-HT(2A) or 5-HT(2C) receptors. In addition, we assayed both groups of compounds as head shake inducers in rats. At the 5-HT(2C) receptor, most compounds were partial agonists for both pathways. Relative efficacy of some phenylisopropylamines was higher for both responses compared with their phenethylamine counterparts, whereas for others, no differences were found. At the 5-HT(2A) receptor, most compounds behaved as partial agonists, but unlike findings at 5-HT(2C) receptors, all phenylisopropylamines were more efficacious than their phenethylamine counterparts. 2,5-Dimethoxyphenylisopropylamine activated only the PLC pathway at both receptor subtypes, 2,5-dimethoxyphenethylamine was selective for PLC at the 5-HT(2C) receptor, and 2,5-dimethoxy-4-nitrophenethylamine was PLA(2)-specific at the 5-HT(2A) receptor. For both receptors, the rank order of efficacy of compounds differed depending upon which response was measured. The phenylisopropylamines were strong head shake inducers, whereas their phenethylamine congeners were not, in agreement with in vitro results and the involvement of 5-HT(2A) receptors in the head shake response. Our results support the concept of functional selectivity and indicate that subtle changes in ligand structure can result in significant differences in the cellular signaling profile.
Assuntos
Anfetaminas/farmacologia , Alucinógenos/farmacologia , Fenetilaminas/farmacologia , Agonistas do Receptor 5-HT2 de Serotonina , 2,5-Dimetoxi-4-Metilanfetamina/análogos & derivados , 2,5-Dimetoxi-4-Metilanfetamina/farmacologia , Animais , Ácido Araquidônico/metabolismo , Comportamento Animal/efeitos dos fármacos , Células CHO , Cricetinae , Cricetulus , Humanos , Fosfatos de Inositol/metabolismo , Masculino , Mescalina/análogos & derivados , Mescalina/farmacologia , Atividade Motora/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Receptor 5-HT2A de Serotonina/genética , Receptor 5-HT2A de Serotonina/fisiologia , Receptor 5-HT2C de Serotonina/genética , Receptor 5-HT2C de Serotonina/fisiologia , Transdução de Sinais/efeitos dos fármacos , TransfecçãoRESUMO
Serotonergic behavioral responses, effects on motor activity and core temperature, and binding properties of the novel putative anxiolytic amphetamine derivative (+/-)1-(2,5-dimethoxy-4-ethylthio-phenyl)-2-aminopropane (ALEPH-2), were examined in rodents in order to elucidate the mechanism underlying its anxiolytic-like effect. After peripheral administration in rats, ALEPH-2 induced some symptoms of the serotonergic syndrome, e.g. forepaw treading and flat body posture. Additionally, a decrease in motor activity was observed. No significant effects on the number of head shakes were observed after injection, although high inter-subject variability was noted. Higher doses of ALEPH-2, in the range exhibiting anxiolytic properties (4mg/kg), elicited significant hypothermia in mice. The affinity of the drug for 5-HT2A/2C receptors ([3H]ketanserin sites) was in the nanomolar range (Ki = 173 nM), whereas for 5-HT1A, benzodiazepine sites, and GABAA receptors, the affinity was micromolar of lower. Based on these results the mechanism of action and the anxiolytic-like properties of ALEPH-2 are discussed.
Assuntos
Ansiolíticos/farmacologia , Comportamento Animal/efeitos dos fármacos , 2,5-Dimetoxi-4-Metilanfetamina/análogos & derivados , 2,5-Dimetoxi-4-Metilanfetamina/administração & dosagem , 2,5-Dimetoxi-4-Metilanfetamina/metabolismo , 2,5-Dimetoxi-4-Metilanfetamina/farmacologia , Análise de Variância , Animais , Ansiolíticos/administração & dosagem , Ansiolíticos/metabolismo , Sítios de Ligação , Temperatura Corporal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Hipotermia/induzido quimicamente , Ketanserina/metabolismo , Masculino , Camundongos , Atividade Motora/efeitos dos fármacos , Ensaio Radioligante , Ratos , Ratos Wistar , Receptores de GABA-A/metabolismo , Receptores de GABA-A/fisiologia , Receptores de Serotonina/metabolismo , Receptores de Serotonina/fisiologia , Antagonistas da Serotonina/metabolismoRESUMO
Behavioral effects of the phenethylamine derivative (+/-)-1-(2,5-dimethoxy-4-ethylthiophenyl)-2-aminopropane (ALEPH-2) were studied in mice and rats. Murine locomotor activity, measured with a photocell actometer, was markedly depressed following IP injection of 2 and 6 mg/kg of the drug. The same doses of the drug also decreased frequency and duration of head dipping and the number of rearings in the hole board apparatus. In the murine elevated plus maze 2 and 6 mg/kg of ALEPH-2 increased the percentage of both open arm entries and time. The total number of entries into the enclosed arms was not significantly affected by the drug. In the rat, 2-12 mg/kg ALEPH-2, IP, decreased photobeam counts in the actometer in a dose-dependent fashion. Both 2 and 4 mg/kg of the drug increased the percentage of open arm entries, but only the highest dose significantly increased the percentage of time spent on the open arms. The dose of 4 mg/kg ALEPH-2 also significantly decreased the total number of enclosed arm entries. Finally, in a recently developed model of anxiety and memory, the elevated T-maze, the doses of 2 and 4 mg/kg ALEPH-2 did not change inhibitory avoidance of the open arms. Nevertheless, the highest dose had an amnestic effect on this task, repeated 72 h later in the absence of drug. In addition, this dose significantly increased the latency to escape from the open arms and had an amnestic effect measured 72 h later. Overall, these results indicate that ALEPH-2 possesses anxiolytic, amnestic as well as sedative and/or motor depressant actions.