Multiple opioid receptors mediate the respiratory depressant effects of fentanyl-like drugs in the rat.

1. Respiratory depressant effects of five drugs of the fentanyl series have been studied in anaesthetised rats. 2. The potency ratios of the fentanyl drugs to produce apnea and depress minute volume were dissimilar. Further, in vivo naloxone pA2 values were identical for blockade of apnea for the fentanyl drugs but different for antagonism of minute volume. 3. Differences in agonist potency and in naloxone pA2 values were also seen in vagotomised rats where only depression of minute volume is observed. 4. The data suggests that multiple receptor interactions are involved in the respiratory depressant effects of these drugs; the apnea response is primarily mediated through peripheral mu receptors but minute volume depression involves both mu receptors and non-mu sites.