Synthesis and cytotoxicity of acetyl-4H,9H-naphtho[2,3-b]thiophene-4,9-diones.

Several new acetyl-4H,9H-naphtho[2,3-b]thiophene-4,9-diones were synthesized and evaluated for in vitro cytotoxicity by NCI against seven cancer cell types. 2,7-Diacetyl naphtho[2,3-b]thiophene-4,9-dione (9) showed significant cytotoxicity against leukemia cells with log GI50 values of -7.61 against SR cells and -7.18 against MOLT-4 cells. 3-Acetyl-naphtho[2,3-b]thiophene-4,9-dione (6) also demonstrated potent cytotoxicity in the latter cell line with log GI50 < -8.

Prolonged analgesia after epidural injection of a poorly soluble salt of fentanyl.

Epidurally administered fentanyl is commonly used in postoperative pain management. The onset of action is rapid, but the duration of analgesia is short. In this study we examined the hypothesis that a poorly soluble salt of fentanyl (fentanyl pamoate) would create a depot of the drug in the epidural space and thus provide prolonged analgesia. The dose-response relationship and duration of analgesic action of epidural fentanyl citrate (FC) and fentanyl pamoate (FP) were studied in white male Sprague-Dawley rats. Somatic and visceral nociceptive stimulation (tail flick and colorectal distension, respectively) were used to test the analgesic effects of the drugs. The calculated dose producing 100% of the maximum possible effect (100% MPE) for FP was 31 micrograms toward somatic and 33 micrograms toward visceral noxious stimulation, and for FC it was 3 micrograms toward both stimulations. The antinociceptive effects were similar, with 31 micrograms of FP and 3 micrograms of FC. The areas under the time-response curves (AUC) were significantly higher with FP than with FC when high doses (5 micrograms of FC or 50 micrograms of FP) were used, but with doses expected to produce 100% MPE, differences between the study drugs were not observed in the duration of analgesia. We conclude that the duration of antinociceptive effect of fentanyl can be prolonged when administered as a poorly soluble salt.