The synthesis and biological evaluation of serotonin (5-HTB1AB) imaging agent [P131PI]- 4-iodo-N-{2-[4-(2-methoxyphenyl)-piperazin-1-yl]-ethyl}-N-pridin-2-yl-benzamide ([P131PI]MPPI ) are reported. The chemical struct...The synthesis and biological evaluation of serotonin (5-HTB1AB) imaging agent [P131PI]- 4-iodo-N-{2-[4-(2-methoxyphenyl)-piperazin-1-yl]-ethyl}-N-pridin-2-yl-benzamide ([P131PI]MPPI ) are reported. The chemical structure of aimed compound and intermediates were confirmed by IR, P1PHNMR, and MS. Radiochemical purity was above 99% determined by TLC. Biodistribution of [P131PI]MPPI in rats displayed high uptake in hippocam-pus and low uptake in cerebellum. The ratio of the uptake of [P131PI]MPPI in hippocampus to that in cerebellum was 2.90 at 30 min post injection. The radioactivity in thyroid was 0.069 and 0.128% ID/g organ at 5 min and 120 min, respectively, and it was increased with time, which suggests that in vivo deiodination may be the major route of me-tabolism. Ex vivo autoradiography of brain section displayed significant decrease of radioactivity in hippocampus when pretreated with 8-OH-DPAT, a selective 5HTB1AB agonist, compared with control. These findings strongly sug-gested that P131PI-MPPI could be used as an in vivo marker for studies of pharmacology of the 5-HTB1AB receptor system in animals.展开更多
基金Supported by grants from National Natural Science Foundation of China (30470496)"135" Medicinal Momentous Project of Jiangsu Province (RC2002068)+1 种基金Jiangsu Natural Science Foundation (BK2004423)Department of Personnel, Jiangsu Province (2003-07).
文摘The synthesis and biological evaluation of serotonin (5-HTB1AB) imaging agent [P131PI]- 4-iodo-N-{2-[4-(2-methoxyphenyl)-piperazin-1-yl]-ethyl}-N-pridin-2-yl-benzamide ([P131PI]MPPI ) are reported. The chemical structure of aimed compound and intermediates were confirmed by IR, P1PHNMR, and MS. Radiochemical purity was above 99% determined by TLC. Biodistribution of [P131PI]MPPI in rats displayed high uptake in hippocam-pus and low uptake in cerebellum. The ratio of the uptake of [P131PI]MPPI in hippocampus to that in cerebellum was 2.90 at 30 min post injection. The radioactivity in thyroid was 0.069 and 0.128% ID/g organ at 5 min and 120 min, respectively, and it was increased with time, which suggests that in vivo deiodination may be the major route of me-tabolism. Ex vivo autoradiography of brain section displayed significant decrease of radioactivity in hippocampus when pretreated with 8-OH-DPAT, a selective 5HTB1AB agonist, compared with control. These findings strongly sug-gested that P131PI-MPPI could be used as an in vivo marker for studies of pharmacology of the 5-HTB1AB receptor system in animals.
