Synthesis and pharmacological characterization of (+/-)-5,9 alpha-dimethyl-2-[2-(4-fluorophenyl)ethyl]-2'-hydroxy-6,7-benzomorphan (fluorophen), a ligand suitable for visualization of opiate receptors in vivo.
A fluorinated derivative of the benzomorphan opiate agonist phenazocine, (+/-)-5,9 alpha-dimethyl-2-[2-(4-fluorophenyl)ethyl]-2'-hydroxy-6, 7-benzomorphan (fluorophen), was prepared by N-acylation of (+/-)-5,9 alpha-dimethyl-2'-hydroxybenzomorphan with (p-fluorophenyl)acetyl chloride, followed by diborane reduction of the resulting amide. Fluorination produces only a twofold opiate receptor affinity loss when measured either by bioassay or receptor binding (selectivity mu congruent to delta greater than kappa). Labeled with 18F, fluorophen should be sufficiently potent to be useful as an in vivo probe for visualizing opiate receptors by positron emission transaxial tomography (PETT).
D000818:Animals; D001575:Benzomorphans / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D001681:Biological Assay; D001921:Brain / Q000378:metabolism; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D007202:Indicators and Reagents; D008297:Male; D009019:Morphinans; D009119:Muscle Contraction / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism*
D001575:Benzomorphans; D007202:Indicators and Reagents; D009019:Morphinans; D011957:Receptors, Opioid; C039571:fluorophen