Pharmacokinetics, systemic toxicity, thermoregulation and acute behavioural effects of 25CN-NBOMe
Jazyk angličtina Země Spojené státy americké Médium print
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
36001433
DOI
10.1111/adb.13216
Knihovny.cz E-zdroje
- Klíčová slova
- 25CN-, NBOMe, Wistar rat, behavioural study, novel psychoactive substances, toxicity,
- MeSH
- fenethylaminy MeSH
- halucinogeny * farmakologie MeSH
- krysa rodu Rattus MeSH
- potkani Wistar MeSH
- termoregulace MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- fenethylaminy MeSH
- halucinogeny * MeSH
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 < 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 < 0.01), increased anxiety (p < 0.05) and 5 mg/kg additionally impaired sensorimotor gating (p < 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.
1st Faculty of Medicine Institute of Pathology Charles University Prague Czech Republic
3rd Faculty of Medicine Charles University Prague Czech Republic
Psychedelics Research Centre National Institute of Mental Health Klecany Czech Republic
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