Characterization of [3H]zetidoline binding to rat striatal membranes.
The binding of [3H]zetidoline, a novel neuroleptic agent, to rat brain striatal membranes was investigated in-vitro. The optimal binding conditions for [3H]zetidoline differed from those for [3H]spiperone in pH, temperature and time. [3H]Zetidoline has high affinity for striatal dopamine receptors. Its binding is saturable, stereo-specific, has a low non-specific component and is reversible and tissue specific. The Scatchard analysis gave a biphasic curve, indicating that [3H]zetidoline interacts with more than one population of receptor sites (B'max = 67 fmol mg-1 protein, K'd = 0.11 nM; B"max = 500 fmol mg-1 protein, K'd = 2.49 nM). Kinetic analysis of rates of association and dissociation yielded a Kd value in agreement with that measured at equilibrium. Inhibition studies indicated that only dopamine and dopaminergic agents are able to displace [3H]zetidoline from its binding sites, and in a different rank order from that for displacement of [3H]spiperone. (-)-Sulpiride was especially effective in inhibiting [3H]zetidoline specific binding. Furthermore, like that of [3H]benzamides, [3H]zetidoline binding appears to be highly Na+-dependent and Li+ only partially substitutes Na+.
Barone
D
D
Assandri
A
A
Galliani
G
G
Glässer
A
A
Tarzia
G
G
D000818:Animals; D014150:Antipsychotic Agents / Q000378:metabolism*; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007093:Imidazoles / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D008094:Lithium / Q000378:metabolism; D008297:Male; D008566:Membranes / Q000378:metabolism; D009928:Organ Specificity; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000378:metabolism; D013134:Spiperone / Q000378:metabolism; D013237:Stereoisomerism; D013696:Temperature; D013997:Time Factors
D014150:Antipsychotic Agents; D007093:Imidazoles; C027277:zetidoline; D013134:Spiperone; D008094:Lithium; D012964:Sodium