Dose- and time-dependent biphasic response to morphine on intestinal migrating myoelectric complex.

We investigated the biphasic response to morphine infusion on migrating myoelectric complex (MMC) cycling in seven conscious dogs. Morphine infusions at the rate of 20, 50, 100, 200, 500 and 1000 micrograms/kg/hr were started at 0 or 40% of MMC cycle and continued for 3 hr in each experiment. All infusion rates starting at 40% of MMC cycle initiated the first postinfusion MMC cycle prematurely (P less than .05). The mean period of the first postinfusion MMC cycle decreased for higher infusion rates. After the first premature MMC cycle, higher infusion rates (500 and 1000 micrograms/kg/hr) inhibited MMC cycling completely whereas the lower infusion rates inhibited MMC cycling in a dose-dependent manner. When infusion was started at 0% of MMC cycle, the first premature MMC cycle occurred consistently only at 20 micrograms/kg/hr. For higher infusion rates, initiation of premature MMC cycle or inhibition of MMC cycling was dose-dependent. Naloxone blocked both the excitatory and the inhibitory effects of morphine on MMC cycling. Morphine infusions also initiated phase III activity in the postprandial state in a dose-dependent manner. Truncal vagotomy and splanchnectomy did not abolish the excitatory or the inhibitory effects of morphine on MMC cycling. We conclude that morphine infusion has a biphasic effect on MMC cycling. The exact nature of the response depends on the dose of morphine and the time in the MMC cycle when infusion is started. Both the excitatory and the inhibitory responses may be mediated through peripheral mu opiate receptors.