Pharmacology of U-91356A, an agonist for the dopamine D2 receptor subtype

• Published in: European journal of pharmacology Vol. 317; no. 1; pp. 29 - 38
• Main Authors: PIERCEY, M. F, MOON, M. W, SETHY, V. H, SCHREUR, P. J. K. D, SMITH, M. W, TANG, A. H, VONVOIGTLANDER, P. F
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier 12.12.1996
• Subjects: Aminoquinolines - metabolism; Aminoquinolines - pharmacology; Animals; Behavior, Animal - drug effects; Binding, Competitive - drug effects; Biological and medical sciences; Brain Chemistry - drug effects; Catecholamines - metabolism; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; Dopamine - biosynthesis; Dopamine Agonists - metabolism; Dopamine Agonists - pharmacology; Electrophysiology; Fundamental and applied biological sciences. Psychology; Imidazoles - metabolism; Imidazoles - pharmacology; Indoles - metabolism; Kinetics; Male; Mice; Mice, Inbred Strains; Quinpirole - metabolism; Rats; Rats, Sprague-Dawley; Receptors, Dopamine D2 - agonists; Receptors, Dopamine D2 - metabolism; Vertebrates: nervous system and sense organs; Agonist; Rodentia; Central nervous system; Autoreceptor; Molecular interaction; In vitro; Biological activity; Mechanism; Postsynaptic; In vivo; Vertebrata; Biological fixation; Mammalia; Spontaneous physical activity; D2 Dopamine receptor; Mouse; Animal; Behavior
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/s0014-2999(96)00695-4

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.