INHIBITION OF CELL-GROWTH AND DNA, RNA, AND PROTEIN-SYNTHESIS INVITRO BY FENTANYL, SUFENTANIL, AND OPIATE ANALGESICS

We have studied the cytotoxic nature of two groups of narcotic analgesics. Group I consists of the opioids, morphine, codeine, hydromorphone, thebaine, and etorphine. Group II contains but two phenylpiperidine-type narcotics, fentanyl and sufentanil. To measure cytotoxicity, three different bioassays were employed using an established line of human cells. Specifically, the effects of narcotic analgesics on DNA, RNA, and protein synthesis were measured by following the uptake and incorporation of radiolabeled thymidine, uridine, and amino acids, respectively. Inhibition of cell growth also was studied by measuring population doubling times of logarithmically growing cells in the presence (or absence) of the test compounds. Lastly, cloning efficiencies of cells were determined in the presence of both groups of compounds. Group I compounds were significantly less inhibitory than Group II compounds by all three bioassays. Moreover, flow cytometric DNA analysis of cells treated with 100 and 320-mu-M etorphine HCl showed essentially no effects on cell cycle distribution. These in vitro results thus suggest that (1) fentanyl and sufentanil are inherently more cytotoxic than the opioid narcotics in Group I, and (2) the highly potent morphinoid drug etorphine HCl appears to have special promise as a transdermal narcotic to control pain.