Effects of zotepine, chlorpromazine and haloperidol on D-1, D-2, D-3 and D-4 subtypes of dopamine receptors in rat striatal and bovine caudate nucleus membranes.
Inhibitory effects of zotepine (Zot) on D-1, D-2, D-3 and D-4 subtypes of dopamine (DA) receptors were investigated in crude synaptic membranes of rat striatum and bovine caudate nucleus and compared to those of chlorpromazine (CPZ) and haloperidol (HAL). From the IC(50)-values of Zot, CPZ and HAL, the K-values of each drug are estimated as follows: 34.4, 152 and 244 nM (D-1, (3)H-labeled cis-flupenthixol binding (1.0 nM) to rat membranes); 37.4, 7.1 and 2.4 nM (D-2, [(3)H]spiperone (Spi) binding (0.5 nM) to rat membranes in the presence of 0.1 ?M ketanserin); 73.1, 15.2 and 22.4 nM (D-3, (3)H-labeled N-propylapomorphine (NPA) binding (0.29 nM) to bovine membranes in the presence of 0.1 ?M Spi); 9.5, 65.3 and 3.1 nM (D-4, [(3)H]NPA binding (0.29 nM) bovine membranes in the presence of 25 nM DA), respectively. Zot binds with higher affinity to D-4 but lower affinity to D-3 than to other subtypes. It is also presumed that Zot binds to D-1 with high affinity and D-2 and D-3 with low affinity compared to CPZ and HAL.
Arima
T
T
Department of Pharmacology, Institute of Pharmaceutical Sciences, Hiroshima University School of Medicine, Kasumi 1-2-3, Minami-ku, Hiroshima 734, Japan.
Makihata
J
J
Makimura
T
T
Nomura
Y
Y
Segawa
T
T