Abstract
Di-isopropylfluorophosphate (DFP) potentiates the antinociceptive activity of alfentanil but has no effect on the activity of morphine or fentanyl. We have studied the effect of DFP on the distribution of these three opioids in the brain. Distribution studies were carried out using 3H-labelled opioids administered subcutaneously to mice. Animals were killed at times of peak antinociceptive activity and 3H-opioid measured in plasma and in eight brain regions. DFP pretreatment (1 mg kg-1) caused a significant increase in the brain:plasma ratio of alfentanil in all brain regions but had no effect on brain:plasma ratios for morphine or fentanyl. The enhanced entry of alfentanil into the brain of DFP-treated mice probably accounts for the increased antinociception observed with this opioid. This drug interaction appears to be opioid specific.
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