Analytical quantification, intoxication case series, and pharmacological mechanism of action for N‐ethylnorpentylone (N‐ethylpentylone or ephylone). Issue 3 (21st October 2018)

• Record Type: Journal Article
• Authors: Costa, Jose Luiz; Cunha, Kelly Francisco; Lanaro, Rafael; Cunha, Ricardo Leal; Walther, Donna; Baumann, Michael H.
• Is Part Of: Drug testing and analysis. Volume 11:Issue 3(2019)
• Page Start: 461
• Page End: 471
• Publication Date: 2018-10-21
• Subjects: forensic toxicology -- liquid chromatography–tandem mass spectrometry -- monoamine transporter -- new psychoactive substances -- synthetic cathinone; Drugs -- Analysis -- Periodicals; Drug testing -- Periodicals; Chemistry, Forensic -- Periodicals; 615.1901
• DOI: 10.1002/dta.2502
• Languages: English
• ISSNs: 1942-7603

Abstract

Abstract: 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 [ 3 H] 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. Abstract : Here, we present a validated method for quantifying the synthetic cathinone, N ‐ethylnorpentylone, in human case work. Blood concentrations of the drug ranged from 7 ‐ 170 ng/mL in intoxicated individuals. N ‐ethylnorpentylone 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 transporters for dopamine and norepinephrine, thereby elevating extracellular levels of these neurotransmitters in the brain and periphery.