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

K. Šíchová, K. Syrová, E. Kofroňová, N. Pinterova-Leca, Č. Vejmola, J. Nykodemová, P. Palivec, L. Olejníková, H. Danda, P. Jorratt, Š. Adam, BQ. Hiep, K. Štefková-Mazochová, M. Končická, M. Kuchař, T. Páleníček

. 2022 ; 27 (5) : e13216. [pub] -

Language English Country United States

Document type Journal Article

Persistent link   https://www.medvik.cz/link/bmc22024492

Grant support
NU21-0400307 Czech Health Research Council
260533/SVV/2021 Czech Ministry of Education, Youth and Sports
20-25349S Czech Science Foundation
RVO00023752 Long-term conceptual development of research organization
PharmaBrainEF16_025/0007444 Operational Programme Research, Development and Education project
VI20172020056 Safety Research under the Czech Ministry of the Interior

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.

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