Opioid-like antinociceptive and locomotor effects of emerging fentanyl-related substances.

Autor: Varshneya NB; Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA, USA., Walentiny DM; Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA, USA., Moisa LT; Department of Pharmacology and Toxicology, Virginia Commonwealth University, 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, Richmond, VA, USA. Electronic address: patrick.beardsley@vcuhealth.org.
Jazyk: angličtina
Zdroj: Neuropharmacology [Neuropharmacology] 2019 Jun; Vol. 151, pp. 171-179. Date of Electronic Publication: 2019 Mar 20.
DOI: 10.1016/j.neuropharm.2019.03.023
Abstrakt: The emergence of several fentanyl-related substances in the recreational drug marketplace has resulted in a surge of opioid overdose deaths in the United States. Many of these substances have never been examined in living organisms under controlled conditions. In the present study, seven fentanyl-related substances were tested in adult male Swiss Webster mice for their effects on locomotion and antinociception and compared to those of fentanyl and morphine. In locomotor activity tests, fentanyl (1, 10 mg/kg), morphine (100, 180 mg/kg), isobutyrylfentanyl (10 mg/kg), crotonylfentanyl (10 mg/kg), para-fluorobutyrylfentanyl (10, 100 mg/kg), para-methoxybutyrylfentanyl (10 mg/kg), thiophenefentanyl (100 mg/kg), and benzodioxolefentanyl (0.1 mg/kg) produced significant (p ≤ 0.05) dose-dependent increases in locomotion. Valerylfentanyl, however, was without effects on locomotion up to 100 mg/kg. In warm-water tail-withdrawal tests, all substances produced significant (p ≤ 0.05) dose-dependent increases in antinociception with increasing ED 50 values (CI) of isobutyrylfentanyl [0.0768 mg/kg (0.044-0.128)] > fentanyl [0.0800 mg/kg (0.0403-0.164)] > para-methoxybutyrylfentanyl [0.106 mg/kg (0.0516-0.195)] > crotonylfentanyl [0.226 mg/kg (0.176-0.292)] > para-fluorobutyrylfentanyl [0.908 mg/kg (0.459-1.58)] > thiophenefentanyl [4.66 mg/kg (3.65-5.95)] > valerylfentanyl [6.43 mg/kg (3.91-10.5)] > morphine [7.82 mg/kg (5.42-11.0)] > benzodioxolefentanyl [46.3 mg/kg (25.8-83.4)]. Naltrexone (1 mg/kg) increased antinociceptive ED 50 values several fold in decreasing magnitudes of isobutyrylfentanyl (233x) > para-methoxybutyrylfentanyl (37.7x) > thiophenefentanyl (34.6x) > valerylfentanyl (11.9x) > para-fluorobutyrylfentanyl (10.9x) > benzodioxolefentanyl (8.42x) > crotonylfentanyl (6.27x) > fentanyl (3.95x) > morphine (1.48x). These findings establish that locomotor and antinociceptive effects of several fentanyl-related substances are similar to those of morphine and fentanyl and are mediated by opioid receptors.
(Copyright © 2019 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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