Chronic haloperidol does not alter agonist affinity for dopamine receptors in vitro.
Agonist competition for [3H]spiperone binding to striatal dopamine D2 receptors was studied in rats rendered supersensitive by chronic treatment with haloperidol. The classical dopamine agonist (-)-N-n-propylnorapomorphine displaced [3H]spiperone biphasically, with IC50 values of 0.5 and 140 nM for the high and low affinity components, respectively. Neither the relative density nor the affinity of either site for (-)-N-propylnorapomorphine was affected by chronic haloperidol treatment. On the other hand, the novel agonist EMD 23 448 displaced [3H]spiperone monophasically. Although this agent only displays potent dopaminergic agonism in supersensitive animals, chronic treatment with haloperidol likewise did not alter the affinity of this drug for [3H]spiperone binding sites. The results suggest that the enhanced in vivo potency of certain agonists in supersensitive animals is probably not mediated by changes in D2 receptor affinity.
Meller
E
E
Bohmaker
K
K
Goldstein
M
M
Schweitzer
J W
JW
Friedhoff
A J
AJ
D000818:Animals; D001058:Apomorphine / Q000031:analogs & derivatives / Q000378:metabolism; D001667:Binding, Competitive; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D006220:Haloperidol / Q000494:pharmacology*; D007211:Indoles / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000378:metabolism; D017448:Receptors, Dopamine D2; D013134:Spiperone / Q000378:metabolism
D007211:Indoles; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D013134:Spiperone; C009074:N-n-propylnorapomorphine; C037307:3-(4-(4-phenyl-1,2,3,6-tetrahydropyridyl-1)-butyl)indole; D006220:Haloperidol; D001058:Apomorphine