N-(3-Fluoropropyl)-N-normetazocine, a potentially useful opiate antagonist for opiate receptor studies with positron emission tomography (PET).
A new fluorinated derivative of N-propylnormetazocine, N-(3-fluoropropyl)-N-normetazocine (1) was synthesized. 1 was similar to the unfluorinated analog 3 in its ability to compete with (3H)-naltrexone for binding sites in rat brain membranes and its potency in antagonizing morphine analgesia in rats. Competition of both compounds against (3H)-naltrexone was little affected by the presence of sodium chloride, a characteristic frequently exhibited by opiate antagonists. Morphine analgesia in rats was measured by suppression of locomotion and vocalization responses to footshock. The ability of 1 to antagonize morphine analgesia in rats was similar to that of 3. Neither 1 nor 3 showed any evidence of agonist activity in rats at doses as high as 1.0 mg/kg (the highest dose tested). These results suggest that 1, labeled with 18F, may be useful for in vivo studies of the opiate receptor using positron emission tomography (PET).
D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism; D003496:Cyclazocine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009271:Naltrexone / Q000378:metabolism; D009292:Narcotic Antagonists / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000032:analysis*; D013329:Structure-Activity Relationship; D014055:Tomography, Emission-Computed
D000700:Analgesics; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D009271:Naltrexone; D009020:Morphine; C047098:N-(3-fluoropropyl)-N-normetazocine; D003496:Cyclazocine