SDZ PSD 958, a novel D1 receptor antagonist with potential limbic selectivity.
SDZ PSD 958, a novel benzo[g]quinoxaline derivative exhibits the properties of a potent orally active selective D1 receptor antagonist. It has high affinity for D1-like receptors (D1, D5; pKi = 9.7-9.8) labelled by [3H]SCH23390 and is at least 400 fold less active at D2-like receptors (i.e. D2, D4) labelled by [3H]spiperone. Effects in functional tests are consistent with D1 receptor antagonist properties. SDZ PSD 958 inhibited apomorphine-induced rearing in mice and prevented prolongation of novelty-induced locomotion in rats elicited by the selective D1 receptor agonist CY 208-243. By contrast, SDZ PSD 958 did not induce catalepsy and only weakly inhibited apomorphine-induced stereotyped gnawing in rats. This suggests that SDZ PSD 958 preferentially inhibits responses mediated by dopamine systems innervating the limbic system.
Markstein
R
R
Sandoz Pharma Ltd., Basle, Switzerland.
Gull
P
P
Rüdeberg
C
C
Urwyler
S
S
Jaton
A L
AL
McAllister
K
K
Dixon
A K
AK
Hoyer
D
D
D000109:Acetylcholine / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001058:Apomorphine / Q000037:antagonists & inhibitors; D001480:Basal Ganglia Diseases / Q000139:chemically induced / Q000503:physiopathology; D002375:Catalepsy / Q000139:chemically induced / Q000523:psychology; D002417:Cattle; D018492:Dopamine Antagonists / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008032:Limbic System / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D011388:Prolactin / Q000097:blood; D011810:Quinoxalines / Q000493:pharmacokinetics / Q000494:pharmacology*; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000037:antagonists & inhibitors*; D012160:Retina / Q000187:drug effects / Q000201:enzymology; D013563:Sympathectomy, Chemical
D018492:Dopamine Antagonists; D011810:Quinoxalines; D017447:Receptors, Dopamine D1; C104716:SDZ PSD 958; D011388:Prolactin; D000262:Adenylyl Cyclases; D001058:Apomorphine; D000109:Acetylcholine