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Synthesis and evaluation of fluorinated derivatives of fentanyl as candidates for opiate receptor studies using positron emission tomography

Abstract

Three fluorinated derivatives of fentanyl, fluorofentanyl (3), keto-fluorofentanyl (5), and fluorofentanol (6), were synthesized and their abilities to compete with /sup 3/diprenorphine for binding sites in guinea pig brain membranes were determined. The relative potencies were fentanyl > 3 approx.= 6 >> 5. On the basis of its apparent affinity for opiate receptors and its relative ease of synthesis, 6 was selected for further study. Fentanyl was slightly better than 6 in its ability to compete with (/sup 3/H)naltrexone for binding sites in rat brain membranes. Both fentayl and 6 exhibited a similar high ''sodium ratio'' (quotient of the IC/sub 50/'s against (/sup 3/H)naltrexone in the presence and absence of sodium chloride) generally characteristic of opiate agonists. The analgesic potencies of fentanyl and 6 were determined in rats by measuring suppression of locomotion and vocalization responses to footshock. 6 appeared slightly less potent than fentanyl, but produced a similar analgesia and catalepsy which was entirely blocked by pretreatment of rats with naloxone, an opiate antagonist. A rapid synthesis of (/sup 18/F)-6 was developed and the tissue distribution of (/sup 18/F)-6 in mice was determined 5, 60, and 120 minutes after intravenous injection. The use of this general route to /sup  More>>
Publication Date:
Mar 01, 1986
Product Type:
Journal Article
Reference Number:
GBN-86-003718; EDB-88-040746
Resource Relation:
Journal Name: J. Labelled Compd. Radiopharm.; (United Kingdom); Journal Volume: 23:3
Subject:
38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEAR CHEMISTRY; NARCOTICS; DISTRIBUTION; LABELLING; ORGANIC FLUORINE COMPOUNDS; RADIOPHARMACEUTICALS; CHEMICAL PREPARATION; FLUORINE 18; MICE; POSITRON COMPUTED TOMOGRAPHY; RECEPTORS; ANIMALS; BETA DECAY RADIOISOTOPES; BETA-PLUS DECAY RADIOISOTOPES; CENTRAL NERVOUS SYSTEM DEPRESSANTS; COMPUTERIZED TOMOGRAPHY; DIAGNOSTIC TECHNIQUES; DRUGS; EMISSION COMPUTED TOMOGRAPHY; FLUORINE ISOTOPES; HOURS LIVING RADIOISOTOPES; ISOTOPES; LABELLED COMPOUNDS; LIGHT NUCLEI; MAMMALS; MEMBRANE PROTEINS; NUCLEI; ODD-ODD NUCLEI; ORGANIC COMPOUNDS; ORGANIC HALOGEN COMPOUNDS; PROTEINS; RADIOISOTOPES; RODENTS; SYNTHESIS; TOMOGRAPHY; VERTEBRATES; 400703* - Radiochemistry & Nuclear Chemistry- Radioisotope Production
OSTI ID:
5735004
Research Organizations:
Brookhaven National Lab., Upton, NY, USA
Country of Origin:
United Kingdom
Language:
English
Contract Number:
AC02-76CH00016
Other Identifying Numbers:
Journal ID: CODEN: JLCRD
Submitting Site:
GBN
Size:
Pages: 277-293
Announcement Date:
Dec 01, 1987

Citation Formats

Hwang, Dahren, Feliu, A L, Wolf, A P, MacGregor, R R, Fowler, J S, and Arnett, C D. Synthesis and evaluation of fluorinated derivatives of fentanyl as candidates for opiate receptor studies using positron emission tomography. United Kingdom: N. p., 1986. Web. doi:10.1002/jlcr.2580230306.
Hwang, Dahren, Feliu, A L, Wolf, A P, MacGregor, R R, Fowler, J S, & Arnett, C D. Synthesis and evaluation of fluorinated derivatives of fentanyl as candidates for opiate receptor studies using positron emission tomography. United Kingdom. https://doi.org/10.1002/jlcr.2580230306
Hwang, Dahren, Feliu, A L, Wolf, A P, MacGregor, R R, Fowler, J S, and Arnett, C D. 1986. "Synthesis and evaluation of fluorinated derivatives of fentanyl as candidates for opiate receptor studies using positron emission tomography." United Kingdom. https://doi.org/10.1002/jlcr.2580230306.
@misc{etde_5735004,
title = {Synthesis and evaluation of fluorinated derivatives of fentanyl as candidates for opiate receptor studies using positron emission tomography}
author = {Hwang, Dahren, Feliu, A L, Wolf, A P, MacGregor, R R, Fowler, J S, and Arnett, C D}
abstractNote = {Three fluorinated derivatives of fentanyl, fluorofentanyl (3), keto-fluorofentanyl (5), and fluorofentanol (6), were synthesized and their abilities to compete with /sup 3/diprenorphine for binding sites in guinea pig brain membranes were determined. The relative potencies were fentanyl > 3 approx.= 6 >> 5. On the basis of its apparent affinity for opiate receptors and its relative ease of synthesis, 6 was selected for further study. Fentanyl was slightly better than 6 in its ability to compete with (/sup 3/H)naltrexone for binding sites in rat brain membranes. Both fentayl and 6 exhibited a similar high ''sodium ratio'' (quotient of the IC/sub 50/'s against (/sup 3/H)naltrexone in the presence and absence of sodium chloride) generally characteristic of opiate agonists. The analgesic potencies of fentanyl and 6 were determined in rats by measuring suppression of locomotion and vocalization responses to footshock. 6 appeared slightly less potent than fentanyl, but produced a similar analgesia and catalepsy which was entirely blocked by pretreatment of rats with naloxone, an opiate antagonist. A rapid synthesis of (/sup 18/F)-6 was developed and the tissue distribution of (/sup 18/F)-6 in mice was determined 5, 60, and 120 minutes after intravenous injection. The use of this general route to /sup 18/F-labeled derivatives of fentanyl for studies of the opiate receptor using positron emission tomography is planned.}
doi = {10.1002/jlcr.2580230306}
journal = []
volume = {23:3}
journal type = {AC}
place = {United Kingdom}
year = {1986}
month = {Mar}
}