D2-dopamine receptor specific brain uptake of carbon-11-labeled YM-09151-2.
The in vivo D2-receptor specific brain uptake of N-[(2RS,3RS)-1-benzyl-2- methyl-3-pyrrolidinyl]-5-chloro-2-methoxy-4-[11C]methylaminobenzamide ([11C]YM-09151-2), was investigated. In rat brain the high uptake of [11C]YM-09151-2 in striatum was displaced with sulpiride, spiroperidol, and YM-09151-2. SCH-23390 and ritanserin, D1-dopamine and S2-serotonin antagonists, showed no effect on the distribution of [11C]YM-09151-2. In the striatum at 60 min, 95% of the radioactivity was detected as [11C]YM-09151-2 by high performance liquid chromatography. On the other hand, 41% of 11C in the plasma at 60 min was observed as metabolites. In vivo autoradiography showed a high uptake of [11C]YM-09151-2 in the striatum and in the nucleus accumbens of rat brain. A high uptake of radioactivity was also found in the canine basal ganglia with positron emission tomography. The uptake was reduced by pretreatment with spiroperidol. The present results demonstrate that [11C]YM-09151-2 is a D2 receptor specific compound and is a potential in vivo tracer for measuring D2 receptors.
Hatano
K
K
Division of Radiopharmaceutical Chemistry, Tohoku University, Sendai, Japan.
Ishiwata
K
K
Kawashima
K
K
Hatazawa
J
J
Itoh
M
M
Ido
T
T
D000818:Animals; D014150:Antipsychotic Agents / Q000378:metabolism / Q000493:pharmacokinetics*; D001549:Benzamides / Q000378:metabolism / Q000493:pharmacokinetics*; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D002250:Carbon Radioisotopes; D002531:Cerebellum / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D004285:Dogs; D008297:Male; D010880:Piperidines / Q000378:metabolism / Q000493:pharmacokinetics; D011877:Radionuclide Imaging; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000378:metabolism*; D017448:Receptors, Dopamine D2; D016713:Ritanserin; D012702:Serotonin Antagonists / Q000378:metabolism / Q000493:pharmacokinetics; D013134:Spiperone / Q000378:metabolism / Q000493:pharmacokinetics; D013469:Sulpiride / Q000378:metabolism / Q000493:pharmacokinetics
D014150:Antipsychotic Agents; D001549:Benzamides; D002250:Carbon Radioisotopes; D010880:Piperidines; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D012702:Serotonin Antagonists; D016713:Ritanserin; D013134:Spiperone; D013469:Sulpiride; C030265:nemonapride