Doses of acetyl salicylic acid and morphine in combination which provided either maximal levels of analgesia or the highest potentiation effect in the rat
✍ Scribed by Francisco J. Lopéz-Muñoz; Carlos M. Villalón; José A. Terrón; Luis A. Salazar
- Publisher
- John Wiley and Sons
- Year
- 1995
- Tongue
- English
- Weight
- 809 KB
- Volume
- 35
- Category
- Article
- ISSN
- 0272-4391
No coin nor oath required. For personal study only.
✦ Synopsis
The analgesic efficacy of the combination of acetyl salicylic acid (ASA), a nonsteroidal anti-inflammatory drug (NSAID), and morphine, a p-opiate receptor agonist, was evaluated in the pain-induced functional impairment in the rat (PIFIR) model. Groups of 6 rats received either vehicle, ASA (175.4, 311.9, 555.1, 986.9, 1,755.2, or 3,121.3 kmol/kg p.0.1, morphine (3.1, 5.5, 9.8, 17.5,31 .1, or 55.2 pmol/kg s.c.), or a combination of ASA and morphine (24 different combinations). This allowed us to detect the profile of analgesic interaction of the combinations. Furthermore, we set out to determine the optimal degree of potentiation obtained with a specific combination of the above drugs by means of the "surface of synergistic interaction" of the combinations. The ED,, values for ASA and morphine were 1,167.9 2 6.7 and 18.4 ? 3.7 pmolikg, respectively. Eleven combinations of ASA and morphine produced a level of analgesia significantly greater than can be accounted for by simple addition of the analgesic effects of each analgesic drug alone ( P < 0.01).
The combination of ASA (3,121.3 pmol/kg) and morphine (31 .I pmol/kg) produced the maximum analgesic effect. However, three combinations of ASA + morphine (555.1 + 31.1, 986.9 + 9.8, and 1,755.2 + 9.8 pmol/kg, respectively) produced the highest potentiation effects ( P < 0.01). The surface of synergistic interaction clearly showed which combination of these analgesic drugs produced the highest degree of potentiation in the rat. This study showed that it i s possible to rationally predict the specific combinations of analgesic drugs and their dosages which will provide either maximal levels of analgesia or the highest potentiation effect in the rat. D 1995 Wilev-Liss, Inc.