Structurally diverse fentanyl analogs yield differential locomotor activities in mice.

Autor: Varshneya NB; Center for Drug Evaluation and Research, Food and Drug Administration, United States Department of Health and Human Services, Silver Spring, MD, USA; Department of Pharmacology and Toxicology, Virginia Commonwealth University School of Medicine, Richmond, VA, USA. Electronic address: nvarshn2@jhmi.edu., Walentiny DM; Department of Pharmacology and Toxicology, Virginia Commonwealth University School of Medicine, Richmond, VA, USA., Stevens DL; Department of Pharmacology and Toxicology, Virginia Commonwealth University School of Medicine, Richmond, VA, USA., Walker TD; Diversion Control Division, Drug Enforcement Administration, United States Department of Justice, Springfield, VA, USA., Akinfiresoye LR; Diversion Control Division, Drug Enforcement Administration, United States Department of Justice, Springfield, VA, USA., Beardsley PM; Department of Pharmacology and Toxicology, Virginia Commonwealth University School of Medicine, Richmond, VA, USA; Center for Biomarker Research & Precision Medicine, Virginia Commonwealth University School of Pharmacy, Richmond, VA, USA.
Jazyk: angličtina
Zdroj: Pharmacology, biochemistry, and behavior [Pharmacol Biochem Behav] 2023 Jan; Vol. 222, pp. 173496. Date of Electronic Publication: 2022 Nov 24.
DOI: 10.1016/j.pbb.2022.173496
Abstrakt: 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.
Competing Interests: Declaration of competing interest Neil B. Varshneya, PhD reports financial support was provided by National Institutes of Health. Patrick M. Beardsley, PhD reports financial support was provided by United States Department of Justice. Teneille D. Walker, PhD reports a relationship with United States Drug Enforcement Administration that includes: employment. Luli R. Akinfiresoye, PhD reports a relationship with United States Drug Enforcement Administration that includes: employment.
(Published by Elsevier Inc.)
Databáze: MEDLINE
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