[H-3] QUINELORANE BINDS TO D-2 AND D-3 DOPAMINE-RECEPTORS IN THE RAT-BRAIN

Quinelorane is a BCD partial ergoline with potent dopaminergic effects in vitro and in vivo. Partial ergoline compounds of this series consi st of the B-, C- and D-rings of the four ring ergoline skeleton. Many of the pharmacological effects of quinelorane are believed to be due t o stimulation of the D-2 subtype of the dopamine receptor. Recently, a D-3 dopamine receptor was identified that is insensitive to guanine n ucleotides and exhibits an unusual distribution in the brain. When thi s receptor is expressed in Chinese hamster ovary cells, quinelorane ha s higher affinity for the D-3 receptor than the D-2 receptor. To furth er define the pharmacology of quinelorane, we have synthesized [H-3]-q uinelorane and examined its binding to sections of rat brain in vitro. [H-3]-quinelorane bound with high affinity (K-D = 1.8 nM) and exhibit ed very low nonspecific binding. D-2 selective antagonists, such as ()butaclamol and spiperone, were potent inhibitors of binding while the D-1 antagonist SCH23390 was significantly less potent. A majority of the binding was inhibited in a concentration-dependent manner by guany lyl-imidodiphosphate with a maximal inhibition at concentrations of 1 mu M and greater. Autoradiographic studies were performed in the prese nce and absence of 10 mu M Gpp(NH)p. Binding in D-2 containing regions , such as the caudate-putamen, was completely inhibited by guanylyl-im idodiphosphate although binding in D-3 containing areas, such as the i slands of Calleja, was unaffected. Therefore, [H-3]-quinelorane is an excellent agonist radioligand for the localization of D-2 and D-3 rece ptors in rat brain.