Structurally diverse fentanyl analogs yield differential locomotor activities in mice

IF 3.3 3区心理学 Q1 BEHAVIORAL SCIENCES

Pharmacology Biochemistry and Behavior Pub Date : 2023-01-01 DOI:10.1016/j.pbb.2022.173496

Neil B. Varshneya , D. Matthew Walentiny , David L. Stevens , Teneille D. Walker , Luli R. Akinfiresoye , Patrick M. Beardsley

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引用次数: 4

Abstract

Synthetic narcotics have been implicated as the single greatest contributor to increases in opioid-related fatalities in recent years. This study evaluated the effects of nine fentanyl-related substances that have emerged in the recreational drug marketplace, and for which there are no existing or only limited in vivo data. Adult male Swiss Webster mice were administered fentanyl-related substances and their effects on locomotion as compared to MOR agonist standards were recorded. In locomotor activity tests, morphine (100, 180 mg/kg), buprenorphine (1, 10 mg/kg), fentanyl (1, 10 mg/kg), cyclopropylfentanyl (1, 10 mg/kg), cyclopentylfentanyl (10 mg/kg), (±)-cis-3-methylbutyrylfentanyl (0.1, 1, 10 mg/kg), ortho-methylacetylfentanyl (10 mg/kg), para-chloroisobutyrylfentanyl (100 mg/kg), ocfentanil (1, 10 mg/kg), and ortho-fluoroacrylfentanyl (0.1, 1, 10 mg/kg) elicited significant (p ≤ 0.05) dose-dependent increases in locomotion. However, 2,2,3,3-tetramethylcyclopropylfentanyl did not have any effects on locomotion, even when tested up to 100 mg/kg, and 4′-methylacetylfentanyl (10, 100 mg/kg) significantly decreased locomotion. The rank order of efficacy for stimulating locomotion (maximum effect as a % of fentanyl's maximum effect) for fentanyl-related substances relative to MOR agonist standards was cyclopropylfentanyl (108.84 ± 20.21) > fentanyl (100 ± 15.3) > ocfentanil (79.27 ± 16.92) > morphine (75.9 ± 14.5) > (±)-cis-3-methylbutyrylfentanyl (68.04 ± 10.08) > ortho-fluoroacrylfentanyl (63.56 ± 19.88) > cyclopentylfentanyl (56.46 ± 8.54) > para-chloroisobutyrylfentanyl (22.44 ± 8.51) > buprenorphine (11.26 ± 2.30) > ortho-methylacetylfentanyl (9.45 ± 2.92) > 2,2,3,3-tetramethylcyclopropylfentanyl (6.75 ± 1.43) > 4′-methylacetylfentanyl (3.47 ± 0.43). These findings extend in vivo results from previous reports documenting additional fentanyl related-related substances that stimulate locomotion similar to known abused opioids while also identifying some anomalies.

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结构不同的芬太尼类似物在小鼠中产生不同的运动活动

近年来，合成毒品被认为是导致阿片类药物相关死亡人数增加的最大因素。这项研究评估了娱乐性药物市场上出现的九种芬太尼相关物质的影响，这些物质没有现有的或只有有限的体内数据。成年雄性瑞士韦伯斯特小鼠服用芬太尼相关物质，并记录其与MOR激动剂标准相比对运动的影响。在运动活性测试中，吗啡（100，180 mg/kg）、丁丙诺啡（1，10 mg/kg，和邻氟丙烯酰芬太尼（0.1，1，10mg/kg）引起运动的显著（p≤0.05）剂量依赖性增加。然而，2，2，3，3-四甲基环丙基芬太尼对运动没有任何影响，即使在高达100 mg/kg的测试中也是如此，4′-甲基乙酰基芬太尼（101100 mg/kg）显著降低了运动。相对于MOR激动剂标准，芬太尼相关物质刺激运动的功效等级（最大功效为芬太尼最大功效的%）为环丙基芬太尼（108.84±20.21）>；芬太尼（100±15.3）>；oc芬太尼（79.27±16.92）>；吗啡（75.9±14.5）>；（±）-顺式-3-甲基丁酰基芬太尼（68.04±10.08）>；邻氟丙烯酰芬太尼（63.56±19.88）>；环戊基戊基（56.46±8.54）>；对氯异丁酰芬太尼（22.44±8.51）>；丁丙诺啡（11.26±2.30）>；邻甲基乙酰芬太尼（9.45±2.92）>；2,2,3,3-四甲基环丙基芬太尼（6.75±1.43）>；4′-甲基乙酰芬太尼（3.47±0.43）。这些发现扩展了先前报告的体内结果，这些报告记录了额外的芬太尼相关物质，这些物质刺激运动，类似于已知的滥用阿片类药物，同时也发现了一些异常。

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来源期刊

Pharmacology Biochemistry and Behavior 医学-行为科学

CiteScore

6.40

自引率

2.80%

发文量

122

审稿时长

38 days

期刊介绍： Pharmacology Biochemistry & Behavior publishes original reports in the areas of pharmacology and biochemistry in which the primary emphasis and theoretical context are behavioral. Contributions may involve clinical, preclinical, or basic research. Purely biochemical or toxicology studies will not be published. Papers describing the behavioral effects of novel drugs in models of psychiatric, neurological and cognitive disorders, and central pain must include a positive control unless the paper is on a disease where such a drug is not available yet. Papers focusing on physiological processes (e.g., peripheral pain mechanisms, body temperature regulation, seizure activity) are not accepted as we would like to retain the focus of Pharmacology Biochemistry & Behavior on behavior and its interaction with the biochemistry and neurochemistry of the central nervous system. Papers describing the effects of plant materials are generally not considered, unless the active ingredients are studied, the extraction method is well described, the doses tested are known, and clear and definite experimental evidence on the mechanism of action of the active ingredients is provided.