Eutylone: mechanism of action, clinical applications and toxicity

General Description

Eutylone is a synthetic cathinone with psychostimulant effects, primarily interacting with monoamine transporters in the brain. Research indicates that it inhibits neurotransmitter uptake at dopamine and norepinephrine transporters, while also exhibiting partial releasing actions at serotonin transporters. Eutylone's potent locomotor activity in mice suggests abuse liability and psychostimulant side-effects in humans. While it has gained popularity as a recreational drug, its use is illegal and highly discouraged due to potential risks and adverse effects. In clinical applications, eutylone is mainly utilized in scientific studies and forensic analysis for its psychoactive properties and detectability in biological samples. Its prevalence in forensic investigations, association with impairments and fatalities, underscores the importance of controlled laboratory use and awareness among law enforcement and medical professionals.

Figure 1. Eutylone

Mechanism of action

Eutylone is a synthetic cathinone that exhibits psychostimulant effects and carries potential risks such as hospitalizations, overdose, and even death. It is structurally similar to methylone, another synthetic cathinone. While limited information is available regarding the pharmacological effects of eutylone, its chemical structure suggests that it interacts with monoamine transporters in the brain. To investigate this hypothesis, researchers conducted in vitro transporter assays using rat brain synaptosomes and in vivo locomotor activity assessments in mice. The results showed that eutylone, along with its structural isomers dibutylone and pentylone, dose-dependently inhibited neurotransmitter uptake at dopamine transporters (DAT) and norepinephrine transporters (NET). However, the inhibition was more potent at DAT than NET. Eutylone and pentylone also inhibited uptake at serotonin transporters (SERT), while dibutylone did not. Furthermore, eutylone and pentylone exhibited weak partial releasing actions at SERT. In terms of locomotor activity, all the drugs stimulated dose-related movement in mice, with eutylone being the most potent and effective. These findings indicate that eutylone is a compound that acts on multiple transporters. It inhibits uptake at DAT and NET but also behaves as a substrate at SERT. The effects of eutylone are similar to those of pentylone, suggesting that eutylone may carry abuse liability and pose risks for psychostimulant side-effects in human users. ¹

Clinical applications

Eutylone is a synthetic stimulant that falls under the category of cathinones and amphetamines. It has gained popularity in the recreational drug market, primarily as a substitute for MDMA or ecstasy. However, it is important to note that the use of Eutylone for recreational purposes is illegal and highly discouraged due to its potential risks and adverse effects. As a research chemical, Eutylone has found applications in scientific studies and forensic analysis. Its psychoactive properties have been studied for their impact on the central nervous system, including interactions with neurotransmitters like dopamine, serotonin, and norepinephrine. In forensic analysis, Eutylone can be detected and identified in biological samples, making it useful for drug testing and toxicology investigations. Its identification and quantification can provide valuable information for law enforcement agencies and medical professionals. It is crucial to emphasize that Eutylone should only be used in controlled laboratory settings by trained professionals for research purposes. Its potential for misuse, addiction, and adverse health effects make it unsuitable for any medical or therapeutic applications. Overall, Eutylone's primary application lies in scientific research, forensic analysis, and drug detection, while its recreational use is illegal and strongly discouraged due to safety concerns. ²

Toxicity

Eutylone is a synthetic stimulant that belongs to the beta-keto-methylenedioxyamphetamines class of novel psychoactive substances. It is currently one of the most popular subclasses of synthetic stimulants. Eutylone emerged as a replacement for N-ethyl pentylone, which was the most encountered synthetic stimulant prior to its federal scheduling in 2018. From January 2019 to April 2020, eutylone was quantitatively confirmed in 83 forensic investigations, including postmortem cases and driving under the influence of drugs cases. It was detected in blood, urine, and tissue samples from cases submitted from 13 states across the United States, with Florida accounting for 60% of the positive cases. The concentration of eutylone in postmortem blood ranged from 1.2 to 11,000 ng/mL, with a mean concentration of 1,020 ng/mL. In driving under the influence of drugs cases, the concentration ranged from 17 to 3,600 ng/mL, with a mean concentration of 942 ng/mL. Further analysis revealed the presence of three eutylone metabolites, including one unique biomarker and one metabolite in common with butylone. It is important for laboratories to be aware of the presence of eutylone in cases involving suspected use of Ecstasy, "Molly," and/or methylenedioxymethamphetamine, as it can cause impairment or contribute to death. In summary, eutylone is a synthetic stimulant with a high prevalence in forensic investigations, and its use has been associated with impairments and fatalities. ³

Reference

1. Glatfelter GC, Walther D, Evans-Brown M, Baumann MH. Eutylone and Its Structural Isomers Interact with Monoamine Transporters and Induce Locomotor Stimulation. ACS Chem Neurosci. 2021 Apr 7;12(7):1170-1177.

2. Gladden RM, Chavez-Gray V, O'Donnell J, Goldberger BA. Notes From the Field: Overdose Deaths Involving Eutylone (Psychoactive Bath Salts) - United States, 2020. MMWR Morb Mortal Wkly Rep. 2022 Aug 12;71(32):1032-1034.

3. Krotulski AJ, Papsun DM, Chronister CW, Homan J, Crosby MM, Hoyer J, Goldberger BA, Logan BK. Eutylone Intoxications-An Emerging Synthetic Stimulant in Forensic Investigations. J Anal Toxicol. 2021 Feb 6;45(1):8-20.