SURFACE OF SYNERGISTIC INTERACTION BETWEEN DIPYRONE AND MORPHINE IN THE PIFIR MODEL

The analgesic effects of dipyrone and morphine administered either sep arately or in 24 different combinations were determined in the ''Pain- Induced Functional Impairment in the Rat'' (PIFIR analgesic model). Th is allowed the detection of the profile of analgesic interaction of th e various combinations. Furthermore, the optimal degree of potentiatio n obtained with a specific combination of the above drugs was determin ed by means of the ''Surface of Synergistic Interaction'' (SSI) of the combinations. This parameter was calculated from the total analgesic effect produced by the combination after having subtracted the analges ic effect produced by each drug alone. Over the dose-ranges used, the analgesic activities of either dipyrone or morphine tended to be small er than those of their respective combinations. Furthermore, 11 combin ations showed various degrees of potentiation (P < 0.05), while the re mainder (13) exhibited additive analgesic effects. The combination of dipyrone (562 mg/kg, sc) and morphine (5.6 mg/kg, sc) produced the max imum analgesic effect. However, dipyrone (178 mg/kg) with morphine (3. 2 mg/kg) produced the highest potentiation effect (P < 0.001). The sur face of synergistic interaction clearly showed which combination of an algesic drugs produced the highest degree of potentiation in the rat. This represents the first study to show that a specific ratio of combi nation of analgesic drugs can produce an optimal potentiation of their analgesic effects. These findings may have important implications for the treatment of pain. (C) 1994 Wiley-Liss, Inc.