Premium
Surface of synergistic interaction between dipyrone and morphine in the PIFIR model
Author(s) -
LópezMuñoz Francisco J.
Publication year - 1994
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430330105
Subject(s) - analgesic , morphine , long term potentiation , pharmacology , chemistry , hot plate , drug , anesthesia , medicine , receptor , biochemistry , mechanical engineering , engineering
The analgesic effects of dipyrone and morphine administered either separately or in 24 different combination were determined in the “Pain‐Induced Functional Impairment in the Rat” (PIFIR analgesic model). This allowed the detection of the profile of analgesic interaction of the various combinations. Furthermore, the optimal degree of potentiation obtained with a specific combination of the above drugs was determined 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 analgesic effect produced by each drug alone. Over the dose‐ranges used, the analgesic activities of either dipyrone or morphine tended to be smaller than those of their respective combinations. Furthermore, 11 combinations showed various degrees of potentiation ( P < 0.05), while the remainder (13) exhibited additive analgesic effects. The combination of dipyrone (562 mg/kg, sc) and morphine (5.6 mg/kg, sc) produced the maximum analgesic effect. However, dipyrone (178 mg/kg) with morphine (3.2 mg/kg) produced the highest potentiation effect ( P < 0.001). The surface of synergistic interaction clearly showed which combination of analgesic drugs produced the highest degree of potentiation in the rat. This represents the first study to show that a specific ratio of combination of analgesic drugs can produce an optimal potentiation of their analgesic effects. These findings may have important implications for the treatment of pain. © 1994 Wiley‐Liss, Inc.