Abstract
The incidence of fatal overdoses has increased worldwide due to the widespread access to illicit fentanyl and its potent analogues. Vaccines offer a promising strategy to reduce the prevalence of opioid use disorders (OUDs) and to prevent toxicity from accidental and deliberate exposure to fentanyl and its derivatives. This study describes the development and characterization of vaccine formulations consisting of novel fentanyl-based haptens conjugated to carrier proteins. Vaccine efficacy was tested against opioid-induced behavior and toxicity in mice and rats challenged with fentanyl and its analogues. Prophylactic vaccination reduced fentanyl- and sufentanil-induced antinociception, respiratory depression, and bradycardia in mice and rats. Therapeutic vaccination also reduced fentanyl intravenous self-administration in rats. Because of their selectivity, vaccines did not interfere with the pharmacological effects of commonly used anesthetics nor with methadone, naloxone, oxycodone, or heroin. These preclinical data support the translation of vaccines as a viable strategy to counteract fentanyl use disorders and toxicity.
| Original language | English |
|---|---|
| Pages (from-to) | 14647-14667 |
| Number of pages | 21 |
| Journal | Journal of Medicinal Chemistry |
| Volume | 63 |
| Issue number | 23 |
| DOIs | |
| State | Published - 10 Dec 2020 |
| Externally published | Yes |
Bibliographical note
Funding Information:This research was supported by the National Institutes of Health under Award Number T32DA007097 (C.B. and B.C.), and under Award Number UG3DA048386 (M.P.) funded through the National Institute on Drug Abuse (NIDA) and the National Institute of Neurological Disorders and Stroke (NINDS). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Publisher Copyright:
© 2020 American Chemical Society.
