Assessment of anaesthetic action of morphine and fentanyl in rats

Abstract

In 150 Sprague-Dawley rats, morphine and fentanyl dose-effect curves were determined for the following three end points - prevention of purposeful movement response to a noxious stimulus (PM), loss of righting reflex (HR), and prevention of heart rate increase to a noxious stimulus (HR). Accordingly, for each agent, three series of experiments were performed with intravenous administration of the following doses: morphine -3-10mg.kg-1 for PM, 3-10mg.kg-1 for HR, 35-55 mg.kg-1 for RR; fentanyl - 5-15 μg.kg-1 for PM, 18-30 μg.kg-1 for RR, 200-400 μg.kg-1 for HR. Dose-effect curves were calculated with the use of probit procedure and potency ratios were determined on the bases of ED50 values, It was found that potency ratios of morphine and fentanyl are different for the studied end points. The ratios of RR ED50 to PM ED50 were 7.8 for morphine vs 2.4 for fentanyl (p < 0.001 ), the ratios of HR ED50 to PM ED50 were 1 and 33, respectively (p < 0.001). These results suggest that blockade of movement response to noxious stimulation (which is usually regarded as an index for analgesic action of opioids) and blockade of heart rate increase to noxious stimulation (which is one of the goals of anaesthesia) is not necessarily induced by intravenous narcotic anaesthetics through the same mechanism. Analgesic potency of intravenous narcotic anaesthetics, determined on the basis of their ability to block movement response to a noxious stimulus, may not reflect the strength of their action regarding such an important component of anaesthesia as autonomic unresponsiveness to surgicat stimulation. © 1983 Canadian Anesthesiologists.