In vitro affinity of piribedil for dopamine D-3 receptor subtypes, an autoradiographic study

Receptor binding autoradiography, using the selective ligand [H-3]7-OH-(R)DPAT (R(+)-2-dipropylamino-7-hydroxy 1,2,3,4-tetrahy dronaphthalene), showed that piribedil is a potent inhibitor at dopamine D-3 receptors in limbic regions (island of Calleja), with affinity (IC50) between 30 and 60 nM. The in vitro IC50 of piribedil for inhibition of [H-3]spiperone binding to receptors of the dopamine D-2-like family (D-2, D-3 and D-4), ranged between 10(-7) and 10(-6) M in different brain regions (medial and lateral caudate putamen, olfactory tubercles, and nucleus accumbens). At the highest concentration tested (10(-5) M) piribedil inhibited dopamine D-1 receptor binding by < 50%. It is concluded that piribedil has 20 times higher affinity for dopamine D-3 than for dopamine (D)-like receptors, and very low affinity for the dopamine D-1 receptor subtype in rat brain. How this pattern of receptor affinity is related to the pharmacological profile of piribedil deserves further investigation.