Neil B. Varshneya , D. Matthew Walentiny , David L. Stevens , Teneille D. Walker , Luli R. Akinfiresoye , Patrick M. Beardsley
{"title":"结构不同的芬太尼类似物在小鼠中产生不同的运动活动","authors":"Neil B. Varshneya , D. Matthew Walentiny , David L. Stevens , Teneille D. Walker , Luli R. Akinfiresoye , Patrick M. Beardsley","doi":"10.1016/j.pbb.2022.173496","DOIUrl":null,"url":null,"abstract":"<div><p><span>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 </span><em>in vivo</em><span><span> data. Adult male Swiss Webster mice were administered fentanyl-related substances and their effects on locomotion as compared to </span>MOR<span> agonist standards were recorded. In locomotor activity tests, morphine (100, 180 mg/kg), buprenorphine<span> (1, 10 mg/kg), fentanyl (1, 10 mg/kg), cyclopropylfentanyl (1, 10 mg/kg), cyclopentylfentanyl (10 mg/kg), (±)-</span></span></span><em>cis</em>-3-methylbutyrylfentanyl (0.1, 1, 10 mg/kg), <em>ortho</em>-methylacetylfentanyl (10 mg/kg), <em>para</em>-chloroisobutyrylfentanyl (100 mg/kg), ocfentanil (1, 10 mg/kg), and <em>ortho</em>-fluoroacrylfentanyl (0.1, 1, 10 mg/kg) elicited significant (<em>p</em><span> ≤ 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) > (±)-</span><em>cis</em>-3-methylbutyrylfentanyl (68.04 ± 10.08) > <em>ortho</em>-fluoroacrylfentanyl (63.56 ± 19.88) > cyclopentylfentanyl (56.46 ± 8.54) > <em>para</em>-chloroisobutyrylfentanyl (22.44 ± 8.51) > buprenorphine (11.26 ± 2.30) > <em>ortho</em>-methylacetylfentanyl (9.45 ± 2.92) > 2,2,3,3-tetramethylcyclopropylfentanyl (6.75 ± 1.43) > 4′-methylacetylfentanyl (3.47 ± 0.43). These findings extend <em>in vivo</em> results from previous reports documenting additional fentanyl related-related substances that stimulate locomotion similar to known abused opioids while also identifying some anomalies.</p></div>","PeriodicalId":19893,"journal":{"name":"Pharmacology Biochemistry and Behavior","volume":"222 ","pages":"Article 173496"},"PeriodicalIF":3.3000,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9845183/pdf/nihms-1859450.pdf","citationCount":"4","resultStr":"{\"title\":\"Structurally diverse fentanyl analogs yield differential locomotor activities in mice\",\"authors\":\"Neil B. Varshneya , D. Matthew Walentiny , David L. Stevens , Teneille D. Walker , Luli R. Akinfiresoye , Patrick M. Beardsley\",\"doi\":\"10.1016/j.pbb.2022.173496\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p><span>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 </span><em>in vivo</em><span><span> data. Adult male Swiss Webster mice were administered fentanyl-related substances and their effects on locomotion as compared to </span>MOR<span> agonist standards were recorded. In locomotor activity tests, morphine (100, 180 mg/kg), buprenorphine<span> (1, 10 mg/kg), fentanyl (1, 10 mg/kg), cyclopropylfentanyl (1, 10 mg/kg), cyclopentylfentanyl (10 mg/kg), (±)-</span></span></span><em>cis</em>-3-methylbutyrylfentanyl (0.1, 1, 10 mg/kg), <em>ortho</em>-methylacetylfentanyl (10 mg/kg), <em>para</em>-chloroisobutyrylfentanyl (100 mg/kg), ocfentanil (1, 10 mg/kg), and <em>ortho</em>-fluoroacrylfentanyl (0.1, 1, 10 mg/kg) elicited significant (<em>p</em><span> ≤ 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) > (±)-</span><em>cis</em>-3-methylbutyrylfentanyl (68.04 ± 10.08) > <em>ortho</em>-fluoroacrylfentanyl (63.56 ± 19.88) > cyclopentylfentanyl (56.46 ± 8.54) > <em>para</em>-chloroisobutyrylfentanyl (22.44 ± 8.51) > buprenorphine (11.26 ± 2.30) > <em>ortho</em>-methylacetylfentanyl (9.45 ± 2.92) > 2,2,3,3-tetramethylcyclopropylfentanyl (6.75 ± 1.43) > 4′-methylacetylfentanyl (3.47 ± 0.43). These findings extend <em>in vivo</em> results from previous reports documenting additional fentanyl related-related substances that stimulate locomotion similar to known abused opioids while also identifying some anomalies.</p></div>\",\"PeriodicalId\":19893,\"journal\":{\"name\":\"Pharmacology Biochemistry and Behavior\",\"volume\":\"222 \",\"pages\":\"Article 173496\"},\"PeriodicalIF\":3.3000,\"publicationDate\":\"2023-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9845183/pdf/nihms-1859450.pdf\",\"citationCount\":\"4\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Pharmacology Biochemistry and Behavior\",\"FirstCategoryId\":\"102\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0091305722001757\",\"RegionNum\":3,\"RegionCategory\":\"心理学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BEHAVIORAL SCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pharmacology Biochemistry and Behavior","FirstCategoryId":"102","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0091305722001757","RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BEHAVIORAL SCIENCES","Score":null,"Total":0}
Structurally diverse fentanyl analogs yield differential locomotor activities in mice
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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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.
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