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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Prolonged antagonism of opioid action with intravenous nalmefene in man.

To identify the opioid antagonist activity of nalmefene and to determine its duration in man, six healthy male subjects were pretreated on separate days with a saline placebo, 0.5 mg, 1 mg, or 2 mg nalmefene intravenously in a randomized double-blind fashion. Opioid challenges with fentanyl, 2 micrograms/kg, then were administered 1, 2, 4, 6, and 8 h afterward. Respiratory depression was monitored by ventilatory and occlusion pressure responses during CO2 rebreathing, while analgesia to experimental pain was identified with the submaximal effort tourniquet ischemia test. One hour following placebo pretreatment, the initial fentanyl dose produced marked respiratory depression. Minute ventilation and occlusion pressure at a PCO2 60 mmHg during rebreathing (VE60 and P(0.1)60) were reduced to 29 and 41% of control, respectively. The slopes of the ventilatory and occlusion pressure responses also decreased significantly to 51 and 55% of control. Respiratory effects were similar with all subsequent fentanyl doses. Pretreatment with 2 mg nalmefene completely prevented the subjective and respiratory effects of fentanyl for the entire 8 h of the experiment. Nalmefene, 1 mg, significantly blunted the fentanyl effects for the same period, but VE60 values at 6 and 8 h were depressed significantly (P less than 0.05) to 66 and 61% of control. The antagonist effects of the lowest nalmefene dose, 0.5 mg, persisted for about 4 h, at which time VE60 was 64% of control. Fentanyl administration produced consistent increases in pain tolerance (44-55% above control) throughout the experiment. Nalmefene pretreatment abolished this analgesic response in a dose-related time course that mirrored the respiratory effects almost exactly.(ABSTRACT TRUNCATED AT 250 WORDS)[1]


  1. Prolonged antagonism of opioid action with intravenous nalmefene in man. Gal, T.J., DiFazio, C.A. Anesthesiology (1986) [Pubmed]
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