Synthesis and binding properties of several new dopaminergic ligands.
Four different heterocyclic dopamine bioisosteres were synthesized. The affinity and selectivity of these compounds for the D-1 and D-2 classes of the dopamine receptor were determined in competition binding experiments using synaptosomal membranes from bovine caudate nuclei and [3H]SCH 23390 (D-1 selective) and [3H]spiperone (D-2 selective) as radioligands. None of these compounds expressed significant affinity for the D-1 receptors, while compounds 3, 4, 2 and 1 in this order of potency strongly competed with [3H]spiperone binding to D-2 receptors under conditions that prevented radioligand binding to serotonin 5HT2 receptors (50 nM ketanserin). Compounds 3 and 4 behave as agonists as judged by the data obtained in competition binding experiments in the presence of Gpp(NH)p, the former (3) expressing a very high affinity for D-2 receptors.
Tuce
Z
Z
Faculty of Chemistry, University of Belgrade, Yugoslavia.
Soskić
V
V
Joksimović
J
J
D000818:Animals; D001667:Binding, Competitive; D002417:Cattle; D018491:Dopamine Agonists / Q000138:chemical synthesis* / Q000378:metabolism; D008024:Ligands; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*
D018491:Dopamine Agonists; D008024:Ligands; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2