Discriminative and analgesic effects of mu and kappa opioids: in vivo pA2 analysis.

This paper illustrates the use of antagonists to study receptor mediation of the discriminative stimulus effects of opioids and to determine if their analgesic effects are mediated in a similar manner. Analysis by pA2 was used to quantify interactions between the opioid antagonist quadazocine and several opioid agonists. Interactions were examined under a drug discrimination procedure and under a tail withdrawal analgesia procedure. Values of pA2 for quadazocine in combination with the kappa agonists bremazocine, ethylketazocine, and U50,488 ranged between 6.1 and 6.4 under the drug discrimination and tail withdrawal procedures. In contrast, the pA2 values for the mu agonists etorphine, fentanyl, and morphine under these procedures ranged between 7.6 and 8.2. The difference between these pA2 values indicates that the affinity of quadazocine for the receptors mediating the effects of the kappa agonists is over one log unit lower than its affinity for the receptors mediating the effects of the mu agonists. This suggests that the discriminative stimulus and analgesic effects of kappa opioid agonists are mediated at the same opioid receptor type, which is different from the type of opioid receptor at which mu agonists produce their discriminative stimulus and analgesic effects.