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The effects of non-narcotic analgesics have been examined, separately and in admixture, on carrageenan-induced hind paw oedema and on yeast-induced hyperalgesia and hyperthermia in adult rats. The efficacy of the drugs was evaluated using the kinetics of drug-receptor interaction. In addition, the hypothesis was tested that the anti-inflammatory, analgesic and antipyretic activities of the drug mixtures used equal the addition of the activities of the individual drugs and could be predicted from their intrinsic activities and affinities. Dose-dependent inhibition of paw oedema, hyperalgesia and hyperthermia was observed after oral administration of acetylsalicylic acid (aspirin), paracetamol, phenacetin (60, 125, 250 and 500 mg.kg--1), and caffeine (12.5, 25, 50 and 100 mg.kf--1). Over the dose-ranges used, the anti-inflammatory activities of paracetamol, phenacetin and caffeine tended to be smaller than that of aspirin. The dose producing a semi-maximal effect for caffeine was lower than that for aspirin which in turn was comparable to that for paracetamol or phenacetin. The analgesic activities of phenacetin and caffeine were classified as stronger than that of aspirin, whereas the efficacy of paracetamol was similar. Paracetamol and aspirin were comparable as antipyretics. The antipyretic activity of phenacetin was higher but that of caffeine was lower than that of aspirin. For caffeine the dose producing a semi-maximal effect was lower than that of aspirin. Within the dose-ranges used, low doses of mixtures of aspirin with either paracetamol, phenacetin or caffeine exhibited anti-inflammatory, analgesic and antipyretic activities which were not different from the activities expected on the basis of addition. Incidentally, at some of the higher dose levels potentiation of the activity of the drugs was found. Low doses of the triple combinations: aspirin + paracetamol + caffeine and aspirin + phenacetin + caffeine showed anti-inflammatory and antipyretic activities which were not different from those expected on the basis of addition, but the activities observed with higher doses of these combinations indicated potentiation. It is concluded that, in the rat, the anti-inflammatory, analgesic and antipyretic activities of dual and triple combinations of aspirin, paracetamol, phenacetin and caffeine at least equal the activities expected on the basis of addition.
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