Pharmacokinetics, systemic toxicity, thermoregulation and acute behavioural effects of 25CN-NBOMe

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023752%3A_____%2F22%3A43920902" target="_blank" >RIV/00023752:_____/22:43920902 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11120/22:43923760 RIV/60461373:22330/22:43925423 RIV/60461373:22810/22:43925423 RIV/00216208:11110/22:10445804

Výsledek na webu

<a href="https://onlinelibrary.wiley.com/doi/10.1111/adb.13216" target="_blank" >https://onlinelibrary.wiley.com/doi/10.1111/adb.13216</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1111/adb.13216" target="_blank" >10.1111/adb.13216</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Pharmacokinetics, systemic toxicity, thermoregulation and acute behavioural effects of 25CN-NBOMe

Popis výsledku v původním jazyce

N-(2-methoxybenzyl)phenethylamines (NBOMes) are a family of potent 5-HT2A agonists containing substances emerging on the illicit drug market as a replacement for N,N-diethyllysergamide (LSD). Despite the increasing use of NBOMes for diagnostic, research and recreational purposes, only a limited number of studies have focussed on their in vivo effect. Here, we investigated pharmacokinetics, systemic toxicity, thermoregulation in individually and group-housed animals, and acute behavioural effects after subcutaneous administration of 2,5-dimethoxy-4-(2-((2-methoxybenzyl)amino)ethyl)benzonitrile (25CN-NBOMe; 0.2, 1, and 5 mg/kg) in Wistar rats. Drug concentration peaked 1 h after the administration of 5 mg/kg in both blood serum and brain tissue with a half-life of 1.88 and 2.28 h, respectively. According to Organisation for Economic Co-operation and Development 423 toxicity assay, the drug is classified into category 3 with a lethal dose of 300 mg/kg and an estimated LD50 value of 200 mg/kg. Histological examination of organs collected from rats injected with the lethal dose revealed subtle pathological changes, highly suggestive of acute cardiovascular arrest due to malignant arrhythmia. Altered thermoregulation after 5 mg/kg was demonstrated by reduced body temperature in individually housed rats (p &lt; 0.01). Behavioural effects assessed by the Open Field test and Prepulse Inhibition of Startle Response revealed that the two lower doses (0.2 and 1 mg/kg) caused a reduction in locomotor activity (p &lt; 0.01), increased anxiety (p &lt; 0.05) and 5 mg/kg additionally impaired sensorimotor gating (p &lt; 0.001). In summary, 25CN-NBOMe readily passes the blood-brain barrier and exhibits a moderate level of toxicity and behavioural effect comparable with other NBOMes.

Název v anglickém jazyce

Pharmacokinetics, systemic toxicity, thermoregulation and acute behavioural effects of 25CN-NBOMe

Popis výsledku anglicky

N-(2-methoxybenzyl)phenethylamines (NBOMes) are a family of potent 5-HT2A agonists containing substances emerging on the illicit drug market as a replacement for N,N-diethyllysergamide (LSD). Despite the increasing use of NBOMes for diagnostic, research and recreational purposes, only a limited number of studies have focussed on their in vivo effect. Here, we investigated pharmacokinetics, systemic toxicity, thermoregulation in individually and group-housed animals, and acute behavioural effects after subcutaneous administration of 2,5-dimethoxy-4-(2-((2-methoxybenzyl)amino)ethyl)benzonitrile (25CN-NBOMe; 0.2, 1, and 5 mg/kg) in Wistar rats. Drug concentration peaked 1 h after the administration of 5 mg/kg in both blood serum and brain tissue with a half-life of 1.88 and 2.28 h, respectively. According to Organisation for Economic Co-operation and Development 423 toxicity assay, the drug is classified into category 3 with a lethal dose of 300 mg/kg and an estimated LD50 value of 200 mg/kg. Histological examination of organs collected from rats injected with the lethal dose revealed subtle pathological changes, highly suggestive of acute cardiovascular arrest due to malignant arrhythmia. Altered thermoregulation after 5 mg/kg was demonstrated by reduced body temperature in individually housed rats (p &lt; 0.01). Behavioural effects assessed by the Open Field test and Prepulse Inhibition of Startle Response revealed that the two lower doses (0.2 and 1 mg/kg) caused a reduction in locomotor activity (p &lt; 0.01), increased anxiety (p &lt; 0.05) and 5 mg/kg additionally impaired sensorimotor gating (p &lt; 0.001). In summary, 25CN-NBOMe readily passes the blood-brain barrier and exhibits a moderate level of toxicity and behavioural effect comparable with other NBOMes.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30103 - Neurosciences (including psychophysiology)

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2022

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Addiction Biology

ISSN

1355-6215

e-ISSN

1369-1600

Svazek periodika

27

Číslo periodika v rámci svazku

5

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

10

Strana od-do

"Article Numbere: 13216"

Kód UT WoS článku

000835717200001

EID výsledku v databázi Scopus

2-s2.0-85137010402