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Analytical quantification, intoxication case series, and pharmacological mechanism of action for N ‐ethylnorpentylone ( N ‐ethylpentylone or ephylone)
Author(s) -
Costa Jose Luiz,
Cunha Kelly Francisco,
Lanaro Rafael,
Cunha Ricardo Leal,
Walther Donna,
Baumann Michael H.
Publication year - 2019
Publication title -
drug testing and analysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.065
H-Index - 54
eISSN - 1942-7611
pISSN - 1942-7603
DOI - 10.1002/dta.2502
Subject(s) - pharmacology , chemistry , cathinone , stimulant , mechanism of action , norepinephrine transporter , designer drug , drug , dopamine transporter , medicine , norepinephrine , transporter , dopamine , in vitro , amphetamine , biochemistry , gene
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 (IC 50 = 37 nM), NET (IC 50 = 105 nM) and SERT (IC 50 = 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.