Z1046: biochemical characterization of its dopaminergic activity.
Affinity of Z1046 for dopamine receptor subtypes, its ability to modulate D1- and D5-mediated AC stimulation and D1-induced cAMP accumulation were evaluated. On D1-like receptors Z1046 and fenoldopam (fen) showed a similar high affinity, being more potent than DP-5,6-ADTN and 5,6-ADTN. For the D2-like receptors, the affinity rank orders were: D2: Z1046 > or = DP-5,6-ADTN > fen = 5,6-ADTN; D3: Z1046 > DP-5,6-ADTN > fen = 5,6-ADTN; D4: Z1046 = DP-5,6-ADTN > fen = 5,6-ADTN. In AC studies the rank order was: Z1046 = fen > DP-5,6-ADTN > 5,6-ADTN. Z1046 was more efficient than fen in stimulating cAMP accumulation. These results make Z1046 an innovative agent combining D1-like and D2-like activities.
Fantoni
M
M
Zambon Group, Bresso, Milan, Italy.
Moriggi
E
E
Bisiani
C
C
Masotto
C
C
Pocchiari
F
F
Semeraro
C
C
D000818:Animals; D001667:Binding, Competitive; D016466:CHO Cells / Q000378:metabolism; D006224:Cricetinae; D000242:Cyclic AMP / Q000378:metabolism; D004298:Dopamine / Q000502:physiology*; D018491:Dopamine Agonists / Q000378:metabolism / Q000494:pharmacology*; D018818:Fenoldopam / Q000378:metabolism; D018374:LLC-PK1 Cells / Q000378:metabolism; D009284:Naphthols / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D017447:Receptors, Dopamine D1 / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D013134:Spiperone / Q000378:metabolism; D013552:Swine
D018491:Dopamine Agonists; D009284:Naphthols; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; C105333:Z1046; D013134:Spiperone; D000242:Cyclic AMP; D018818:Fenoldopam; D004298:Dopamine