Hallucinogen-Like Action of the Novel Designer Drug 25I-NBOMe and Its Effect on Cortical Neurotransmitters in Rats

Herian, Monika; Wojtas, Adam; Kamińska, Katarzyna; Świt, Paweł; Wach, Anna; Gołembiowska, Krystyna

doi:10.1007/s12640-019-00033-x

Cited by 39 publications

(46 citation statements)

References 66 publications

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“…Therefore, these results suggest that this compound has a common and alarming feature with them. These results are in line with previous studies showing an increased ex vivo striatal DA levels (Jeon et al, 2019) as well as an increased DA transmission in cortical areas of male rats (Herian et al, 2019). Moreover, 25I-NBOMe seems to act differently on DA and 5-HT levels in male and female rats, highlighting sex differences that might influence the frequency of ingestion, as well as the psychoactive effects and the long-term effects.…”

Section: I-nbome Affects the Dopaminergic Transmission In The Nac Ssupporting

confidence: 92%

“…The MDMA-like action of 25I-NBOMe has been also confirmed in vitro since it acts inhibiting the monoamine reuptake transporters with different IC 50 (hSERT, IC 50 = 4.3 µM; hDAT, IC 50 = 75 µM; hNET, IC 50 = 19 µM) in HEK 293 cells (Zwartsen et al, 2017). Recently, it has been demonstrated that this compound increases dopamine (DA) and serotonin (5-HT) in the frontal cortex of male Wistar-Han rats when administered at 3 mg/kg subcutaneously (Herian et al, 2019). Moreover, DA levels in mice synaptosomal striatal fractions were increased by in vitro administration of this substance, and male mice showed an increased conditioned place preference when injected with 25I-NBOMe (0.3 mg/kg, i.p.)…”

Section: Introductionmentioning

confidence: 75%

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Neurochemical and Behavioral Profiling in Male and Female Rats of the Psychedelic Agent 25I-NBOMe

et al. 2019

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4-Iodo-2,5-dimethoxy-N-(2-methoxybenzyl)phenethylamine (25I-NBOMe), commonly called "N-Bomb," is a synthetic phenethylamine with psychedelic and entactogenic effects; it was available on the Internet both as a legal alternative to lysergic acid diethylamide (LSD) and as a surrogate of 3,4-methylenedioxy-methamphetamine (MDMA), but now it has been scheduled among controlled substances. 25I-NBOMe acts as full agonist on serotonergic 5-HT2A receptors. Users are often unaware of ingesting fake LSD, and several cases of intoxication and fatalities have been reported. In humans, overdoses of "N-Bomb" can cause tachycardia, hypertension, seizures, and agitation. Preclinical studies have not yet widely investigated the rewarding properties and behavioral effects of this compound in both sexes. Therefore, by in vivo microdialysis, we evaluated the effects of 25I-NBOMe on dopaminergic (DA) and serotonergic (5-HT) transmissions in the nucleus accumbens (NAc) shell and core, and the medial prefrontal cortex (mPFC) of male and female rats. Moreover, we investigated the effect of 25I-NBOMe on sensorimotor modifications as well as body temperature, nociception, and startle/prepulse inhibition (PPI). We showed that administration of 25I-NBOMe affects DA transmission in the NAc shell in both sexes, although showing different patterns; moreover, this compound causes impaired visual responses in both sexes, whereas core temperature is heavily affected in females, and the highest dose tested exerts an analgesic effect prominent in male rats. Indeed, this drug is able to impair the startle amplitude with the same extent in both sexes and inhibits the PPI in male and female rats. Our study fills the gap of knowledge on the behavioral effects of 25I-NBOMe and the risks associated with its ingestion; it focuses the attention on sex differences that might be useful to understand the trend of consumption as well as to recognize and treat intoxication and overdose symptoms.Neuropharmacology of the Synthetic Hallucinogen 25I-NBOMe Miliano et al.

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Section: I-nbome Affects the Dopaminergic Transmission In The Nac Ssupporting

confidence: 92%

Section: Introductionmentioning

confidence: 75%

Neurochemical and Behavioral Profiling in Male and Female Rats of the Psychedelic Agent 25I-NBOMe

et al. 2019

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“…Rodent studies have suggested reinforcing effects for NBOMe derivatives that involve the dopaminergic system (Custodio et al 2019;Seo et al 2019). The NBOMe derivative 4-iodo-2,5-dimethoxy-N-(2-methoxybenzyl)phenethylamine (25I-NBOMe) was shown to increase extracellular dopamine, 5-HT, and glutamate levels in the rat frontal cortex (Herian et al 2019), but unknown are the ways in which these findings translate to humans.…”

Section: Mechanism Of Action Of Phenethylaminesmentioning

confidence: 99%

Designer drugs: mechanism of action and adverse effects

2020

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Psychoactive substances with chemical structures or pharmacological profiles that are similar to traditional drugs of abuse continue to emerge on the recreational drug market. Internet vendors may at least temporarily sell these so-called designer drugs without adhering to legal statutes or facing legal consequences. Overall, the mechanism of action and adverse effects of designer drugs are similar to traditional drugs of abuse. Stimulants, such as amphetamines and cathinones, primarily interact with monoamine transporters and mostly induce sympathomimetic adverse effects. Agonism at l-opioid receptors and c-aminobutyric acid-A (GABA A) or GABA B receptors mediates the pharmacological effects of sedatives, which may induce cardiorespiratory depression. Dissociative designer drugs primarily act as N-methyl-D-aspartate receptor antagonists and pose similar health risks as the medically approved dissociative anesthetic ketamine. The cannabinoid type 1 (CB 1) receptor is thought to drive the psychoactive effects of synthetic cannabinoids, which are associated with a less desirable effect profile and more severe adverse effects compared with cannabis. Serotonergic 5-hydroxytryptamine-2A (5-HT 2A) receptors mediate alterations of perception and cognition that are induced by serotonergic psychedelics. Because of their novelty, designer drugs may remain undetected by routine drug screening, thus hampering evaluations of adverse effects. Intoxication reports suggest that several designer drugs are used concurrently, posing a high risk for severe adverse effects and even death.

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“…The HTR is widely used as a behavioral marker for hallucinogen effects in humans (Halberstadt and Geyer, 2018). 25C-NBOMe, 25I-NBOMe, and 25B-NBOMe induced an HTR response in rodents with a potency several-fold higher than their 2C counterparts, 2C-C and 2C-I (Halberstadt and Geyer, 2014;Elmore et al, 2018;Custodio et al, 2019;Herian et al, 2019). Two lines of evidence support a notion that this behavioral effect is mediated by cortical 5-HT 2A receptors.…”

Section: Pharmacology Of Nbomesmentioning

confidence: 89%

“…DOI also increased the dopamine level in the cortex and ventral tegmental area (VTA) (Bortolozzi et al, 2005;Pehek et al, 2006). Recently, Herian et al (2019), using microdialysis in freely moving male Wistar-Han rats, demonstrated increased extracellular levels of glutamate, dopamine, and 5-HT in the frontal cortex after administration of 25I-NBOMe. The drug also increased the tissue content of 5-HT and its metabolite hydroxyindoleacetic acid (5-HIAA) but did not affect the tissue content of dopamine and its metabolites: 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanilic acid (HVA).…”

Section: Pharmacology Of Nbomesmentioning

confidence: 99%

NBOMes–Highly Potent and Toxic Alternatives of LSD

2020

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Recently, a new class of psychedelic compounds named NBOMe (or 25X-NBOMe) has appeared on the illegal drug market. NBOMes are analogs of the 2C family of phenethylamine drugs, originally synthesized by Alexander Shulgin, that contain a N-(2-methoxy)benzyl substituent. The most frequently reported drugs from this group are 25I-NBOMe, 25B-NBOMe, and 25C-NBOMe. NBOMe compounds are ultrapotent and highly efficacious agonists of serotonin 5-HT 2A and 5-HT 2C receptors (Ki values in low nanomolar range) with more than 1000-fold selectivity for 5-HT 2A compared with 5-HT 1A. They display higher affinity for 5-HT 2A receptors than their 2C counterparts and have markedly lower affinity, potency, and efficacy at the 5-HT 2B receptor compared to 5-HT 2A or 5-HT 2C. The drugs are sold as blotter papers, or in powder, liquid, or tablet form, and they are administered sublingually/buccally, intravenously, via nasal insufflations, or by smoking. Since their introduction in the early 2010s, numerous reports have been published on clinical intoxications and fatalities resulting from the consumption of NBOMe compounds. Commonly observed adverse effects include visual and auditory hallucinations, confusion, anxiety, panic and fear, agitation, uncontrollable violent behavior, seizures, excited delirium, and sympathomimetic signs such mydriasis, tachycardia, hypertension, hyperthermia, and diaphoresis. Rhabdomyolysis, disseminated intravascular coagulation, hypoglycemia, metabolic acidosis, and multiorgan failure were also reported. This survey provides an updated overview of the pharmacological properties, pattern of use, metabolism, and desired effects associated with NBOMe use. Special emphasis is given to cases of nonfatal and lethal intoxication involving these compounds. As the analysis of NBOMes in biological materials can be challenging even for laboratories applying modern sensitive techniques, this paper also presents the analytical methods most commonly used for detection and identification of NBOMes and their metabolites.

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Hallucinogen-Like Action of the Novel Designer Drug 25I-NBOMe and Its Effect on Cortical Neurotransmitters in Rats

Cited by 39 publications

References 66 publications

Neurochemical and Behavioral Profiling in Male and Female Rats of the Psychedelic Agent 25I-NBOMe

Neurochemical and Behavioral Profiling in Male and Female Rats of the Psychedelic Agent 25I-NBOMe

Designer drugs: mechanism of action and adverse effects

NBOMes–Highly Potent and Toxic Alternatives of LSD

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