Comparative effects of analgesics on pain threshold, respiratory frequency and gastrointestinal propulsion.

In the rat, the ratio of the analgesic to the respiratory depressant potency was the same for morphine, codeine, diamorphine, methadone, dipipanone, piperidylisomethadone, phenadoxone, dextromoramide, and propoxyphene. The relative respiratory depressant activity of pethidine tended to be less, but the difference was not significant. The ratio of the analgesic dose to the dose preventing transport of a charcoal meal in the rat was about the same for morphine, codeine, pethidine, methadone, phenadoxone, dimethylthiambutene, and propoxyphene; the relative activities of these compounds in inhibiting the peristaltic reflex of the isolated guinea-pig ileum were also similar. However, because of differences in the slopes of regression lines in the charcoal meal test, some compounds (for example, morphine) had a greater effect on gastrointestinal propulsion than others (for example, pethidine) when given at moderate analgesic dose levels.In studies of the effects of intracisternal morphine in the rat, effects on the spinal reflex of the tail were to some extent dissociated from effects on the threshold for a squeak response. Further, the delaying of transport of a charcoal meal paralleled depression of respiratory rate, and this is evidence for the participation of a central as well as a peripheral action in the effect of morphine on the gastrointestinal tract. The delay in propulsion was reduced by nalorphine and increased by atropine and two general anaesthetic substances, but was unaffected by a number of other pharmacological agents.