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

Abstract U-91356A [( R )-5,6-dihydro-5-(propylamino)4 H -imidazo[4,5,1- ij ]quinolin-2-(1 H )-one, monohydrochloride], bound with highest affinity to the dopamine D 2 receptor subtype, although it also bound with somewhat lower affinities to the dopamine D 3 and D 4 , as well as the 5-HT 1A 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 D 2 receptor subtype as a dopamine autoreceptor and as a stimulatory, postsynaptic dopamine receptor.