Narcotics and Diabetes. II. Streptozotocin-induced Diabetes Selectively Alters the Potency of Certain Narcotic Analgesics. Mechanism of Diabetes: Morphine Interaction

The antinociceptive potencies of phenazocine and levorphanol were altered similarly to that of morphine in streptozotocin (STZ)-induced diabetic and transiently hyper- or hypoglycemic mice, but the potencies of methadone, propoxyphene and meperidine were not altered by changes in serum glucose levels. The acute, s.c. LD50 of morphine in STZ-induced diabetic mice was significantly lower than in the control mice, but the acute s.c. LD50 of methadone was not altered by STZ-induced diabetes. By using morphine as the prototype drug for subsequent experiments, it was demonstrated that the potency of naloxone in antagonizing the effects of morphine in te tail-flick test was not altered in diabetics. Levels of morphine in the brains of STZ-induced diabetic mice were not significantly different from control mice. The durations of action of morphine in STZ-induced diabetes and control mice were similar. We conclude that changes in serum glucose levels can selectively alter the potency of certain narcotic analgesics. The interaction between STZ-induced diabetes and morphine-induced antinociception does not appear to be due to differences in the absorption, distribution or elimination of morphine between diabetic and nondiabetic mice.