Case Report

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American Journal of Emergency Medicine

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American Journal of Emergency Medicine 33 (2015) 1843.e1-1843.e3

Severe poisoning after self-reported use of

2-(4-iodo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine, a novel substituted amphetamine: a case series?

Abstract

Significant toxicity from amphetamine and cathinone derivatives is being increasingly reported. We describe a series of self-reported expo- sures to 2-(4-iodo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl] ethanamine (25-I-NBOME or 25-I), a novel amphetamine derivative. Ten patients with an average age of 17 years presented to local emer- gency departments (EDs) in our community after ingestion and/or in- sufflation of a drug referred to as “25-I.” Of 10 patients, 6 reported taking 25-I alone; other substances included ethanol; 2,5-dimethoxy- 4-ethylphenethylamine; marijuana; and ketamine. Most common effects included tachycardia (90%), hypertension (70%), agitation (60%), and hallucinations (50%). The average heart rate was 123 beats per minute. Two patients were found in status epilepticus, and another was found unresponsive. One patient who had a seizure had multiple, discrete Intraparenchymal hemorrhages and acute kidney injury. Six patients were admitted to the intensive care unit, two were treated in the ED and released, and 1 each was admitted to psychiatry or managed in a clinical decision unit and subsequently discharged. Three patients re- quired emergent intubation, and all admitted patients (7/10) were given intravenous benzodiazepines for sedation. Urine and blood specimens were obtained from 1 patient, which showed analytic confirmation of 25-I. In addition to sympathomimetic effects, methoxy and other sub- stituent groups impart serotonergic effects, resulting in hallucinogenic properties. 2-(4-iodo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl) methyl]ethanamine appears to be extremely potent with a reported “dose” of 500 ug resulting in increased potential for inadvertent overdose. This case series describes significant morbidity in a local cluster of young patients after self-reported use of 25-I, a newly identified drug of abuse.

Abuse of novel synthetic amphetamine and cathinone (phenethylamine) derivatives continues to be reported [1-12]. To avoid legal action or criminal prosecution, new synthetic compounds are made by altering the chemical structure from those which have been designated at schedule I [13-15]. Traditional drug screens will not identify most phenethylamines, and comprehensive Laboratory analysis is not available at most hospitals. Over the past several years, many case reports of substituted amphetamine or cathinone drugs have re- ported severe poisonings [4,6,9]. In many of these cases, the diagnosis

? An abstract of this data was presented at the North American Congress of Clinical Toxicology annual meeting held in Las Vegas, NV, 2012.

is presumptive, as laboratory assessment to identify such products is not timely or widely available.

The purpose of this aritcle is to describe a local cluster of self-reported exposures to 2-(4-iodo-2,5-dimethoxyphenyl)-N-[(2 methoxyphenyl) methyl]ethanamine (25-I-NBOME or 25-I) (Figure), a novel am- phetamine derivative. laboratory confirmation of 25-I was confirmed in 1 patient’s serum by high-pressure liquid chromatography with tandem mass spectrometry.

Ten patients with mean age of 17 years (14-20 years), 8 males and 2 females, presented to local emergency departments (EDs) in our community after reported ingestion and/or insufflation of 25-I. Of 10, 6 reported 25-I alone. Four patients admitted to co-ingestion of ethanol; 2,5-dimethoxy-4-ethylphenethylamine; marijuana; or ketamine. The most common clinical effects were tachycardia (90%), hypertension (90%), hyperglycemia (90%), agitation (70%), and hallucinations (50%) (Table). Mean heart rate was 123 beats per minute. Two patients were found in status epilepticus, and another was unresponsive. One patient with seizures also had multiple discrete intraparenchymal cerebral hemorrhages and acute kidney injury. Hyperthermia was not docu- mented in any case. Eight patients with available complete blood cell count results had mean White blood cell counts of 19 913 cells/uL. Sixty percent were admitted to the intensive care unit, 2 were treated in the ED and released, and 1 each was admitted to psychiatry or managed in a clinical decision unit and subsequently discharged. Three patients required emergent intubation, and all admitted patients (7/10) were given intravenous benzodiazepines for sedation. All patients were discharged in good condition once symptoms resolved. Mean Time to discharge was 14 hours (range, 2-36 hours) for uncompli- cated patients. For more complicated cases, the mean time to discharge was 3 days (range, 2-5 days). Blood was analyzed from 1 agitated and tachycardic patient using high-pressure liquid chromatography with tandem mass spectrometry, revealing a serum 25-I (25-I-NBOMe) concentration of 0.76 ng/mL.

In this case series, most patients presented with a sympathomimetic toxidrome. Benzodiazepines were effective in treating tachycardia and agitation. The duration of toxicity was usually less than 24 hours in un- complicated cases. Laboratory confirmation of 25-I was only made in 1 case, although 2 other cases with similar effects presented at the same time from the same party.

2-(4-iodo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl] ethanamine is known on the “street” as N-Bomb, Smiles, Solaris, and Cimbi-5 [3]. However, 25-I is chemically classified as an N-benzyl phenyl- ethylamine 2C derivative, which is a potent 5-HT_2A receptor agonist [4]. 2-(4-iodo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]

0735-6757/(C) 2015

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abuse can be treated with benzodiazepines and intravenous fluids initially. If needed, other adjunctive therapies can be added including antipsychotics, dexmedetomidine, ketamine, propofol, ? blockers, and Calcium-channel blockers [21].

This case series describes significant morbidity after self-reported use of 25-I, a newly identified drug of abuse in a cluster of young patients. All patients in this series responded to benzodiazepines and supportive care.

Figure. Structure of 25-I (25-I-NBOMe).

ethanamine was used in the early 2000s to investigate the effects of 5- HT_2A agonists in mammalian brains [16,17]. Addition of the N-benzyl substitution to the phenylethylamine backbone (2,5-dimethoxy-4- iodophenethylamine or 2C-I) results in enhanced potency, even at sub-milligram doses [16]. Hallucinations can be present with doses of

50 to 150 ug, which is slightly less potent than lysergic acid diethylamide [18]. Effects can be seen within 15 to 20 minutes of use of NBOMe. Plateau effects are seen in 2 to 4 hours with duration of 4 to 6 hours after intranasal use or 6 to 10 hours for buccal or sublin- gual use [18]. More recently in 2013, a case series from England demon- strated the pro-serotonergic and stimulant effects of 25-I [4]. Previously reported clinical effects after 25-I exposure include euphoria, hallu- cinations, empathic feelings, change in level of consciousness, tachy- cardia, hypertension, hyperthermia, nausea, agitation, aggression, insomnia, hallucinations, paranoia, seizures, clonus, hyperglycemia, leukocytosis, elevated creatine kinase levels, metabolic acidosis, rhabdomyolysis, renal failure, and death [3,4,7,17,19].

The chemical composition of designer drugs can change quickly. Sources of synthetic amphetamine congeners may be local clandestine laboratories in addition to the internet and retail outlets. Using diverse substituents will yield different potencies, pharmacokinetics, and either subtle or dramatic differences in clinical presentations. Newly synthe- sized drugs are designed to avoid criminal prosecution because many of these substituted phenethylamines have not yet been scheduled. In July 2012, 9 2C hallucinogens, MDPV (methylenedioxypyrovalerone), mephedrone, and most Synthetic cannabinoids were designated as class I under the Food and Drug Administration Safety and Innovation Act [20].

Given the lack of experience with this new drug of abuse, treatment recommendations should intuitively be similar to those for other substituted amphetamines. Supportive care with intravenous fluids and intubation if needed as well as symptom-based treatment for hy- perthermia, agitation, tachycardia, hypertension, hyperthermia, acute kidney injury, and rhabdomyolysis commonly seen with amphetamine

Table

Clinical effect in 10 cases of 25-I intoxication

No. Mean Range

M.A. Hieger, DO?

S.R. Rose, PharmD

K.L. Cumpston, DO

P.E. Stromberg, MD Division of Clinical Toxicology Department of Emergency Medicine VCU Medical Center, Richmond, VA Virginia Poison Center, Richmond, VA Department of Emergency Medicine VCU Medical Center, Richmond, VA

?Corresponding author. Division of Clinical Toxicology

Department of Emergency Medicine, VCU Medical Center

Virginia Poison Center, Richmond, VA

E-mail address: [email protected]

S. Miller, DO Department of Emergency Medicine VCU Medical Center, Richmond, VA

B.K. Wills, DO Division of Clinical Toxicology Department of Emergency Medicine VCU Medical Center, Richmond, VA Virginia Poison Center, Richmond, VA Department of Emergency Medicine VCU Medical Center, Richmond, VA

http://dx.doi.org/10.1016/j.ajem.2015.04.065

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