Inflamed tissue has a lower
pH value (~5–7) than non-inflamed tissue (7.4).[4] Through
computer simulation, scientists found a way to make the fentanyl analog only affect inflamed tissue via the addition of
fluorine to the chemical structure. In experiment, it was shown that NFEPP produced injury-restricted analgesia in rats with different types of inflammatory pain without exhibiting typical opiate effects, including
respiratory depression,
sedation,
constipation, and chemical seeking behavior.[5][6][7]
As a result, NFEPP has the potential to reduce
opioid addiction and dependency, as there is no effect on users who are not actually suffering from
pain, as the chemical does not interact with non-inflamed brain tissue until much higher doses are reached.[8]
References
^Drug Enforcement Administration Do (February 2018). "Schedules of Controlled Substances:Temporary Placement of Fentanyl-Related Substances in Schedule I. Temporary amendment; temporary scheduling order". Federal Register. 83 (25): 5188–92.
PMID29932611.
^Massaly N, Temp J, Machelska H, Stein C (December 2020). "Uncovering the analgesic effects of a pH-dependent mu-opioid receptor agonist using a model of nonevoked ongoing pain". Pain. 161 (12): 2798–2804.
doi:
10.1097/j.pain.0000000000001968.
PMID32639370.
S2CID220410251.
^Degro CE, Jiménez-Vargas NN, Tsang Q, Yu Y, Guzman-Rodriguez M, Alizadeh E, et al. (June 2023). "Evolving acidic microenvironments during colitis provide selective analgesic targets for a pH-sensitive opioid". Pain. 164 (11): 2501–2515.
doi:
10.1097/j.pain.0000000000002956.
PMC 10731875.
PMID37326658.