Therapeutic and Prophylactic Vaccines to Counteract Fentanyl Use Disorders and Toxicity.
Animals
Bacterial Proteins
/ chemistry
Cattle
Diphtheria Toxin
/ chemistry
Female
Fentanyl
/ immunology
Haptens
/ chemistry
Hemocyanins
/ chemistry
Male
Mice, Inbred BALB C
Opioid-Related Disorders
/ prevention & control
Piperidines
/ chemical synthesis
Proof of Concept Study
Rats, Sprague-Dawley
Serum Albumin, Bovine
/ chemistry
Sufentanil
/ immunology
Vaccines
/ immunology
Journal
Journal of medicinal chemistry
ISSN: 1520-4804
Titre abrégé: J Med Chem
Pays: United States
ID NLM: 9716531
Informations de publication
Date de publication:
10 12 2020
10 12 2020
Historique:
pubmed:
21
11
2020
medline:
4
2
2021
entrez:
20
11
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33215913
doi: 10.1021/acs.jmedchem.0c01042
pmc: PMC8193686
mid: NIHMS1710797
doi:
Substances chimiques
Bacterial Proteins
0
Diphtheria Toxin
0
Haptens
0
Piperidines
0
Vaccines
0
Serum Albumin, Bovine
27432CM55Q
Hemocyanins
9013-72-3
Sufentanil
AFE2YW0IIZ
keyhole-limpet hemocyanin
FV4Y0JO2CX
Fentanyl
UF599785JZ
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
14647-14667Subventions
Organisme : NIDA NIH HHS
ID : T32 DA007097
Pays : United States
Organisme : NIDA NIH HHS
ID : UG3 DA048386
Pays : United States
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