The dopamine D2 agonists RU 24213 and RU 24926 are also kappa-opioid receptor antagonists

The di-(phenethyl)-amine derivatives, RU 24213 and RU 24926 are widely used as selective dopamine D2-receptor agonists. Binding studies now show that they also have affinity for the kappa-opioid receptor. Their affinity is not greatly reduced in the presence of NaCl/GTP, suggesting an antagonist action. This is confirmed for RU 24926, the more active of the two, using the field-stimulated rabbit vas-deferens. With respect to the mu-receptor, RU 24926 shows low binding affinity and also an antagonist effect. These results demonstrate kappa- as well as mu-antagonist activity in a novel chemical series. Moreover, since the kappa-receptor may regulate dopamine release, the results of experiments using these compounds as dopamine D2 agonists should be interpreted with caution.