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.
Fortin
M
M
Centre de Recherches Roussel Uclaf, Romainville, France.
Degryse
M
M
Petit
F
F
Hunt
P F
PF
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000818:Animals; D001575:Benzomorphans / Q000494:pharmacology; D015259:Dopamine Agents / Q000494:pharmacology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D015394:Molecular Structure; D009020:Morphine / Q000037:antagonists & inhibitors; D009292:Narcotic Antagonists; D010627:Phenethylamines / Q000494:pharmacology*; D011759:Pyrrolidines / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu
D001575:Benzomorphans; D015259:Dopamine Agents; D009292:Narcotic Antagonists; D010627:Phenethylamines; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; C027247:MR 2266; C025254:RU 24926; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; C016868:N-n-propyl-N-phenylethyl-4(3-hydroxyphenyl)ethylamine hydrochloride; D009020:Morphine