In vivo binding of 3H-N-methylspiperone to dopamine and serotonin receptors.
3H-N-methylspiperone (3H-NMSP) was used to label dopamine-2 and serotonin-2 in vivo in the mouse. The striatum/cerebellum binding ratio reached a maximum of 80 eight hours after intravenous administration of 3H-NMSP. The frontal cortex/cerebellum ratio was 5 one hour after injection. The binding of 3H-NMSP was saturable in the frontal cortex and cerebellum between doses of 10 and 1,000 micrograms/kg. Between 0.01 and 10 micrograms/kg the ratio total/nonspecific binding increased from 14 to 21. Inhibition of 3H-NMSP binding in the frontal cortex and striatum by ketanserin, a selective serotonin-2 antagonist, demonstrated that 20% of the total binding in the striatum was to serotonin-2 receptors and 91% of the total binding in the frontal cortex was to serotonin-2 receptors. Compared to 3H-spiperone, 3H-NMSP results in a much higher specific/nonspecific binding ratio in the striatum and frontal cortex and displays more than a two-fold higher brain uptake.
D000818:Animals; D002531:Cerebellum / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005625:Frontal Lobe / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D011954:Receptors, Dopamine / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000378:metabolism*; D012995:Solubility; D013134:Spiperone / Q000031:analogs & derivatives* / Q000378:metabolism; D014316:Tritium
D011954:Receptors, Dopamine; D011985:Receptors, Serotonin; D014316:Tritium; D013134:Spiperone; C039167:3-N-methylspiperone