Pharmacokinetics, systemic toxicity, thermoregulation and acute behavioural effects of 25CN‐NBOMe
Klára Šíchová, Kateřina Syrová, Edita Kofroňová, Nikola Pinterová, Čestmír Vejmola, Jitka Nykodemová, Petr Palivec, Lucie Olejníková, Hynek Danda, Pascal Jorratt, Adam Šafanda, Bui Quang Hiep, Kristýna Štefková, Markéta Končická, Martin Kuchař, Tomáš Páleníček
Addiction Biology August 4, 2022 DOI: 10.1111/adb.13216 via OpenAlex
Summary
25CN-NBOMe, a substance related to LSD, readily crosses the blood-brain barrier in rats. After a 5 mg/kg dose, drug concentration peaked in blood and brain at 1 hour, with half-lives of 1.88 and 2.28 hours. The drug is classified as toxicity category 3, with a lethal dose of 300 mg/kg and an estimated LD50 of 200 mg/kg. Histological findings suggest acute cardiovascular arrest from malignant arrhythmia at lethal doses. A 5 mg/kg dose reduced body temperature in individually housed rats. Lower doses (0.2 and 1 mg/kg) reduced locomotor activity and increased anxiety, while 5 mg/kg also impaired sensorimotor gating. The drug's behavioral effects are comparable to other NBOMes.
Study at a glance
| Characteristics | Animal study Peer reviewed |
|---|---|
| Population | Wistar rats |
| Intervention | 25CN-NBOMe |
| Dose | 0.2, 1, and 5 mg/kg |
| Keywords | Thermoregulation Pharmacology Acute toxicity Pharmacokinetics Internal medicine |
| Citations | 8 |
| Key finding | 25CN-NBOMe readily crosses the blood-brain barrier, exhibits moderate toxicity with an LD50 of 200 mg/kg, and alters thermoregulation and behavior in rats. |
Abstract
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.