Psychopharmacology · 2026
Exploring the addictive potential of α-methylfentanyl and acetyl-α-methylfentanyl in animal models.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Xu Deli, Shi Xuesong, Li Kaixi, Kuai Lixin, Luo Xuwen, Chen Yuanyuan, Di Bin, Xu Peng
Аннотация
BACKGROUND: The abuse profiles of α-methylfentanyl and acetyl-α-methylfentanyl remain poorly characterized in preclinical models. This study systematically evaluated their addiction-related behaviours and underlying pharmacological features.
METHODS: Conditioned place preference (CPP) was tested in mice with gradient doses of fentanyl, α-methylfentanyl and acetyl-α-methylfentanyl. Intravenous self-administration, behavioural economic demand curves, cue- and drug-primed reinstatement, and drug discrimination assays were conducted in rats. ED₅₀ values were calculated and compared across compounds.
RESULTS: All three compounds induced significant CPP, with acetyl-α-methylfentanyl showing ~ 30-fold lower potency. In self-administration, all compounds produced inverted U-shaped dose-response curves, with peak infusion rates at 0.5 µg/kg/infusion. Fentanyl exhibited the highest essential value (EV) in demand curve analysis, indicating stronger reinforcing efficacy. A single naloxone pretreatment significantly attenuated both cue- and drug-primed reinstatement. Drug discrimination ED₅₀ was 11.06, 12.65 and 128.3 µg/kg for fentanyl, α-methylfentanyl and acetyl-α-methylfentanyl, respectively.
CONCLUSIONS: α-methyl substitution selectively reduces reinforcing efficacy without altering reward perception; acetylation attenuates both reward and discriminative stimulus effects while preserving reinforcing capacity. µ-Opioid receptor signalling mediates relapse-like behaviour, supporting long-acting antagonists as potential interventions.
METHODS: Conditioned place preference (CPP) was tested in mice with gradient doses of fentanyl, α-methylfentanyl and acetyl-α-methylfentanyl. Intravenous self-administration, behavioural economic demand curves, cue- and drug-primed reinstatement, and drug discrimination assays were conducted in rats. ED₅₀ values were calculated and compared across compounds.
RESULTS: All three compounds induced significant CPP, with acetyl-α-methylfentanyl showing ~ 30-fold lower potency. In self-administration, all compounds produced inverted U-shaped dose-response curves, with peak infusion rates at 0.5 µg/kg/infusion. Fentanyl exhibited the highest essential value (EV) in demand curve analysis, indicating stronger reinforcing efficacy. A single naloxone pretreatment significantly attenuated both cue- and drug-primed reinstatement. Drug discrimination ED₅₀ was 11.06, 12.65 and 128.3 µg/kg for fentanyl, α-methylfentanyl and acetyl-α-methylfentanyl, respectively.
CONCLUSIONS: α-methyl substitution selectively reduces reinforcing efficacy without altering reward perception; acetylation attenuates both reward and discriminative stimulus effects while preserving reinforcing capacity. µ-Opioid receptor signalling mediates relapse-like behaviour, supporting long-acting antagonists as potential interventions.