Analytical quantification, intoxication case series, and pharmacological mechanism of action for N-ethylnorpentylone (N-ethylpentylone or ephylone)

Autor(es)

Costa, Jose Luiz ^{[1, 2]} ; Cunha, Kelly Francisco ^[2] ; Lanaro, Rafael ^[2] ; Cunha, Ricardo Leal ^{[3, 4]} ; Walther, Donna ^[5] ; Baumann, Michael H. ^[5]

Afiliação do(s) autor(es)

^[1] Univ Estadual Campinas, Fac Pharmaceut Sci, BR-13083859 Campinas, SP - Brazil

^[2] Univ Estadual Campinas, Fac Med Sci, Campinas Poison Control Ctr, BR-13083859 Campinas, SP - Brazil

^[3] Univ Fed Bahia, Inst Chem, BR-40170115 Salvador, BA - Brazil

^[4] Inst Anal & Forens Res, BR-49100000 Aracaju, Sergipe - Brazil

^[5] NIDA, Designer Drug Res Unit, Intramural Res Program, NIH, Baltimore, MD - USA

• Tipo de documento: Artigo Científico
• Fonte: DRUG TESTING AND ANALYSIS; v. 11, n. 3, p. 461-471, MAR 2019.
• Citações Web of Science: 4

Resumo

Synthetic cathinones continue to proliferate in clandestine drug markets worldwide. N-ethylnorpentylone (also known as N-ethylpentylone or ephylone) is a popular emergent cathinone, yet little information is available about its toxicology and pharmacology. Here we characterize the analytical quantification, clinical presentation, and pharmacological mechanism of action for N-ethylnorpentylone. Liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) was used to quantify N-ethylnorpentylone in blood obtained from human cases. Clinical features exhibited by the intoxicated individuals are described. The activity of N-ethylnorpentylone at plasma membrane transporters for dopamine (DAT), norepinephrine (NET) and 5-HT (SERT) was assessed using in vitro assays measuring uptake inhibition and evoked release of {[}H-3] neurotransmitters in rat brain synaptosomes. Our LC-MS/MS method assayed N-ethylnorpentylone concentrations with limits of detection and quantification of 1 and 5 ng/mL, respectively. Quantitation was linear from 5 to 500 ng/mL, and the method displayed specificity and reproducibility. Circulating concentrations of N-ethylnorpentylone ranged from 7 to 170 ng/mL in clinical cases, and the associated symptoms included palpitations, tachycardia, agitation, hallucinations, coma and death. N-Ethylnorpentylone was a potent inhibitor at DAT (IC50 = 37 nM), NET (IC50 = 105 nM) and SERT (IC50 = 383 nM) but displayed no transporter releasing activity. We present a validated method for quantifying N-ethylnorpentylone in human case work. The drug is a psychomotor stimulant capable of inducing serious cardiovascular and neurological side-effects which can be fatal. In vitro findings indicate that N-ethylnorpentylone exerts its effects by potent blockade of DAT and NET, thereby elevating extracellular levels of dopamine and norepinephrine in the brain and periphery. (AU)

• Processo FAPESP: 18/00432-1 - A Toxicologia das Novas Substâncias Psicoativas (NSP): epidemiologia do consumo através da análise de amostras de cabelo e fluido oral
• Beneficiário: José Luiz da Costa
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 15/10650-8 - Estudo da estabilidade de fármacos, drogas de abuso e praguicidas em amostras de sangue seco em papel, e sua aplicação na toxicologia forense
• Beneficiário: José Luiz da Costa
• Modalidade de apoio: Auxílio à Pesquisa - Regular