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 in vivo studies of the opiate receptor using positron emission tomography (PET).