Pharmacology of U-91356A, an agonist for the dopamine D2 receptor subtype.
U-91356A [(R)-5,6-dihydro-5-(propylamino)4H-imidazo[4,5,1-ij]quinolin -2-(1H)-one, monohydrochloride], bound with highest affinity to the dopamine D2 receptor subtype, although it also bound with somewhat lower affinities to the dopamine D3 and D4, as well as the 5-HT1A receptor subtypes. In addition to depressing dopamine synthesis and turnover, injection of U-91356A increased striatal acetylcholine concentrations. U-91356A also depressed firing rates of dopamine neurons. In mice, this compound stimulated cage climbing and locomotor activity in reserpinized animals; it also antagonized D-amphetamine-stimulated locomotor activity. It produced contralateral turning in rats with unilateral lesions of the substantia nigra. These data are consistent with roles for the dopamine D2 receptor subtype as a dopamine autoreceptor and as a stimulatory, postsynaptic dopamine receptor.
Piercey
M F
MF
Pharmacia and Upjohn, Inc., Kalamazoo, MI 49001, USA.
Moon
M W
MW
Sethy
V H
VH
Schreur
P J
PJ
Smith
M W
MW
Tang
A H
AH
Von Voigtlander
P F
PF
D000634:Aminoquinolines / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001667:Binding, Competitive / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D002395:Catecholamines / Q000378:metabolism; D004298:Dopamine / Q000096:biosynthesis; D018491:Dopamine Agonists / Q000378:metabolism / Q000494:pharmacology*; D004594:Electrophysiology; D007093:Imidazoles / Q000378:metabolism / Q000494:pharmacology*; D007211:Indoles / Q000378:metabolism; D007700:Kinetics; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D019257:Quinpirole / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000819:agonists* / Q000378:metabolism
D000634:Aminoquinolines; D002395:Catecholamines; D018491:Dopamine Agonists; D007093:Imidazoles; D007211:Indoles; D017448:Receptors, Dopamine D2; C083374:5-propylamino-5,6-dihydro-4H-imidazo(4,5,1-ij)quinolin-2(1H)-one; D019257:Quinpirole; D004298:Dopamine