Test for Respiratory Depression

Respiratory depression is one of the most prominent adverse effects of p opioid agonists (e.g., morphine). The frequency of breathing and the inspiratory volume can be affected differently by drugs and have to be measured. 

Three animals are used for the test compound and the standard. Dose-response curves of the effect on respiratory frequency and volume are compared. While p, opioid agonists decrease respiratory function, k opioid agonist either increase or have no effect on respiratory function. The magnitude of respiratory depression produced by p, opioid agonists is related to their efficacy at opioid receptors with low efficacy agonists such as nalbuphine having much less effect on respiration as compared to morphine. 

Nelson and Elliott (1967) compared the effects of morphine, morphinone and thebaine on respiration and 

Ling et al. (1983,1985) measured blood gas values (p02, PC02, pH) in unrestrained rats via an arterial cannula. p02 and pH decreased whereas pC02 increased after morphine. 

Studies in rhesus monkeys have compared the respiratory depressant effects of opioids to their effects on other behavior (Howell et al. 1988 Butelman et al. 1993 Gerak et al. 1994). 

---