In vitro affinity of piribedil for dopamine D3 receptor subtypes, an autoradiographic study.
Receptor binding autoradiography, using the selective ligand [3H]7-OH-(R)DPAT (R(+)-2-dipropylamino-7-hydroxy 1,2,3,4-tetrahydronaphthalene), showed that piribedil is a potent inhibitor at dopamine D3 receptors in limbic regions (island of Calleja), with affinity (IC50) between 30 and 60 nM. The in vitro IC50 of piribedil for inhibition of [3H]spiperone binding to receptors of the dopamine D2-like family (D2, D3 and D4), 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 D1 receptor binding by < 50%. It is concluded that piribedil has 20 times higher affinity for dopamine D3 than for dopamine D2-like receptors, and very low affinity for the dopamine D1 receptor subtype in rat brain. How this pattern of receptor affinity is related to the pharmacological profile of piribedil deserves further investigation.
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
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Cagnotto
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Parotti
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Mennini
D000818:Animals; D001345:Autoradiography; D001552:Benzazepines / Q000378:metabolism; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D018491:Dopamine Agonists / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D010891:Piribedil / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000378:metabolism*; D013764:Tetrahydronaphthalenes
D001552:Benzazepines; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; D013764:Tetrahydronaphthalenes; D010891:Piribedil; C031349:7-hydroxy-2-N,N-dipropylaminotetralin