Assessment of the antinociceptive, respiratory-depressant, and reinforcing effects of the low pK fluorinated fentanyl analogs, FF3 and NFEPP.

Rationale: Recent studies report that fentanyl analogs with relatively low pK values produce antinociception in rodents without other mu opioid-typical side effects due to the restriction of their activity to injured tissue with relatively low pH values. However, it is unclear if and to what degree these compounds may produce mu opioid-typical side effects (respiratory depression, reinforcing effects) at doses higher than those required to produce antinociception.

Objectives: The present study compared the inflammatory antinociceptive, respiratory-depressant, and reinforcing effects of fentanyl and two analogs of intermediate (FF3) and low (NFEPP) pK values in terms of potency and efficacy in male and female Sprague-Dawley rats.