An evaluation method for developing abuse-deterrent opioid formulations with agonist and antagonist combinations using conditioned place preference.

Autor: Zhang X; Division of Behavioral Neuropharmacology, International Center for Brain Science (ICBS), Fujita Health University, Toyoake, 470-1192, Aichi, Japan., Kitaichi K; Laboratory of Pharmaceutics, Department of Biomedical Pharmaceutics, Gifu Pharmaceutical University, Gifu, 501-1196, Gifu, Japan., Mouri A; Department of Regulatory Science for Evaluation and Development of Pharmaceuticals and Devices, Graduate School of Health Sciences, Fujita Health University, Toyoake, 470-1192, Aichi, Japan; Japanese Drug Organization of Appropriate Use and Research, Nagoya, 468-0069, Aichi, Japan., Zhou X; Division of Behavioral Neuropharmacology, International Center for Brain Science (ICBS), Fujita Health University, Toyoake, 470-1192, Aichi, Japan., Nabeshima T; Japanese Drug Organization of Appropriate Use and Research, Nagoya, 468-0069, Aichi, Japan; Laboratory of Health and Medical Science Innovation, Graduate School of Health Sciences, Fujita Health University, Toyoake, 470-1192, Aichi, Japan., Yamada K; Japanese Drug Organization of Appropriate Use and Research, Nagoya, 468-0069, Aichi, Japan; Department of Neuropsychopharmacology and Hospital Pharmacy, Graduate School of Medicine, Nagoya University, Nagoya, 466-8560, Aichi, Japan., Nagai T; Division of Behavioral Neuropharmacology, International Center for Brain Science (ICBS), Fujita Health University, Toyoake, 470-1192, Aichi, Japan. Electronic address: taku.nagai@fujita-hu.ac.jp.
Jazyk: angličtina
Zdroj: Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2023 Jan 08; Vol. 639, pp. 100-105. Date of Electronic Publication: 2022 Nov 30.
DOI: 10.1016/j.bbrc.2022.11.072
Abstrakt: Although opioids are useful narcotic analgesics in clinical settings, their misuse and addiction in the United States of America and other countries are rapidly increasing. Therefore, the development of abuse-deterrent formulations is an urgent issue. We herein investigated how to select the ratio of an opioid and the opioid receptor antagonist, naloxone in abuse-deterrent formulations for mice. The conditioned place preference (CPP) test was used to evaluate the rewarding effects of abused drugs. The opioids morphine (30 μmol/kg), oxycodone (3 μmol/kg), fentanyl (0.4 μmol/kg), and buprenorphine (0.5 μmol/kg) significantly induced place preference in mice. We also examined the optimal ratio of naloxone and opioids to inhibit the rewarding effects of the latter. Naloxone (3-5 μmol/kg) effectively inhibited place preference induced by the opioids tested. We calculated theoretical drug doses that exerted the same pharmacodynamic effects based on two parameters: μ-opioid receptor binding affinity and blood-brain barrier (BBB) permeability. Theoretical doses were very close to the drug doses at which mice showed place preference. Therefore, the CPP test is useful as a behavioral method for evaluating abuse-deterrent formulations of opioids mixed with an antagonist. The ratio of naloxone with opioids, at which mice did not show place preference, may be an effective index for developing abuse-deterrent formulations. Ratios may be calculated for other opioids based on μ-opioid receptor binding affinity and BBB permeability.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that may have influenced the work reported in this manuscript.
(Copyright © 2022 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: