Sigma1 and dopamine D2 receptor occupancy in the mouse brain after a single administration of haloperidol and two dopamine D2-like receptor ligands.
We investigated sigma(1) and dopamine D(2) receptor occupancy in mouse brain after a single injection of haloperidol, nemonapride, or spiperone using [(11)C]SA4503 and [(11)C]raclopride, respectively. Co-injection of the three compounds significantly blocked the uptake of each radioligand. Six hours later, only haloperidol blocked [(11)C]SA4503 uptake, while all three reduced [(11)C]raclopride uptake. Sigma(1) receptor occupancy by haloperidol was reduced to 19% at day 2 when D(2) receptor occupancy disappeared. [(11)C]SA4503 would be applicable to the investigation of sigma(1) receptor occupancy of antispychotic drugs using PET.
Ishiwata
Kiichi
K
Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, 1-1 Naka-cho, Itabashi-ku, Tokyo 173-0022, Japan. ishiwata@pet.tmig.or.jp
Kawamura
Kazunori
K
Kobayashi
Tadayuki
T
Matsuno
Kiyoshi
K
D000818:Animals; D001549:Benzamides / Q000493:pharmacokinetics / Q000494:pharmacology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D018492:Dopamine Antagonists / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D004347:Drug Interactions; D006220:Haloperidol / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D008024:Ligands; D008297:Male; D051379:Mice; D018697:Nootropic Agents / Q000493:pharmacokinetics / Q000494:pharmacology; D010879:Piperazines / Q000493:pharmacokinetics* / Q000494:pharmacology; D020891:Raclopride / Q000493:pharmacokinetics* / Q000494:pharmacology; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D017480:Receptors, sigma / Q000819:agonists* / Q000378:metabolism
D001549:Benzamides; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D008024:Ligands; D018697:Nootropic Agents; D010879:Piperazines; D017448:Receptors, Dopamine D2; D017480:Receptors, sigma; D020891:Raclopride; C101789:SA 4503; D006220:Haloperidol; C030265:nemonapride