Objective To determine the changes of brain dopamine transporter in mice receiving propofol anesthesia, 125I-β-CIT binding sites were observed at different time course. Methods 1. Twenty-seven normal Kunming mice wer...Objective To determine the changes of brain dopamine transporter in mice receiving propofol anesthesia, 125I-β-CIT binding sites were observed at different time course. Methods 1. Twenty-seven normal Kunming mice were randomizedly divided into 3 groups (n = 9 ) and received intraperitoneal injection of propofol 100, 200 mg/kg and 10% intralipid (as control ) respetively. The time of losing righting reflex and displaying excitatory symptoms were recorded within 10min after administration. 2. Sixty Kunming mice were randomizedly assigned into 2 groups (n = 30 ). The mice were given 125I-β-CIT intravenously and propofol 200mg/kg or 10% intralipid (as control ) intraperitoneally. Five mice in every group were killed at different time course and their brain removed to isolate cerebellar, hypothalamus, striatum and cerebral cones. After weighting brain tissues, the radioactivity of 125I-β-CIT in different brain tissue was measured. Results 1. The time of losing righting reflex wes reduced from 319. 167 ± 88. 228s in proud 100mg/kg group to 231. 667 ± 46. 233s in propofol 200mg/kg group, and it fell from 193. 75 ± 27. 233s to 145. 556 ± 27. 437s for presenting excitatory activity. 2. Propofol intraperitoneal groups significantly decreed the combination of 125I-β-CIT and dopamine transporter in the striatum (P< 0. 01 ) and cerebral cortex (P < 0. 05) 120min after injection of propofol compared with the control group. But propofol increased the binding (P< 0. 05 ) in the striatum 30min after injection. theclusion The inhibitive effect of propofol on dopamine transporter to uptake dopamine in mice brain may contribute to some anesthetic mechanisms.展开更多
To prepare 125/131I-β-CIT (2β-carbomethoxy-β- (4-iodophenyl)tropane) as an imaging agent for dopamine transporter (DAT), the labeling method from tributylstannyl precursor with peracetic acid has been reported in t...To prepare 125/131I-β-CIT (2β-carbomethoxy-β- (4-iodophenyl)tropane) as an imaging agent for dopamine transporter (DAT), the labeling method from tributylstannyl precursor with peracetic acid has been reported in this article. The radio-chemical purity (RCP) of the labeled compound was over 95% determined by HPLC and TLC. The stability, partition coefficients were also determined. The pharmacological studies of the imaging agent were performed in rats, mice, rabbits and normal monkey. The ligand showed preferable uptake in brain (1 .9%ID/organ in rats and 4.5%ID/organ in mice at 5 min). The ratios of striatum/cerebellum, hippocampus/cerebellum and cortex/cerebellum were 28.9, 3.97 and 4.75 at 6 h in rats, and 8.52, 2.99 and 3.06 at 6h in mice, respectively. In monkey brain imaging the ratios of striatum/frontal cortex (ST/FC) and striatum/occipital cortex (ST/OC) were 5.14 and 5.97 at 4 h, respectively. All of above showed the high affinity of the ligand to DAT. The compound was primarily metabo lized in liver because the hepatic uptake was much higher than other organs (75.4%ID/organ at 18h). The half-life of blood elimination was 5min The dose received by mice was 2500 times as high as that received by human in the test of undue toxicity, which evaluated the safety of the agent. All the results suggest that fl-CIT can be used as a potential DAT imaging agent.展开更多
文摘Objective To determine the changes of brain dopamine transporter in mice receiving propofol anesthesia, 125I-β-CIT binding sites were observed at different time course. Methods 1. Twenty-seven normal Kunming mice were randomizedly divided into 3 groups (n = 9 ) and received intraperitoneal injection of propofol 100, 200 mg/kg and 10% intralipid (as control ) respetively. The time of losing righting reflex and displaying excitatory symptoms were recorded within 10min after administration. 2. Sixty Kunming mice were randomizedly assigned into 2 groups (n = 30 ). The mice were given 125I-β-CIT intravenously and propofol 200mg/kg or 10% intralipid (as control ) intraperitoneally. Five mice in every group were killed at different time course and their brain removed to isolate cerebellar, hypothalamus, striatum and cerebral cones. After weighting brain tissues, the radioactivity of 125I-β-CIT in different brain tissue was measured. Results 1. The time of losing righting reflex wes reduced from 319. 167 ± 88. 228s in proud 100mg/kg group to 231. 667 ± 46. 233s in propofol 200mg/kg group, and it fell from 193. 75 ± 27. 233s to 145. 556 ± 27. 437s for presenting excitatory activity. 2. Propofol intraperitoneal groups significantly decreed the combination of 125I-β-CIT and dopamine transporter in the striatum (P< 0. 01 ) and cerebral cortex (P < 0. 05) 120min after injection of propofol compared with the control group. But propofol increased the binding (P< 0. 05 ) in the striatum 30min after injection. theclusion The inhibitive effect of propofol on dopamine transporter to uptake dopamine in mice brain may contribute to some anesthetic mechanisms.
基金Supported by the National Natural Science Foundation of China (39770230), Science Foundation of Health Ministry (98-1-326) and H
文摘To prepare 125/131I-β-CIT (2β-carbomethoxy-β- (4-iodophenyl)tropane) as an imaging agent for dopamine transporter (DAT), the labeling method from tributylstannyl precursor with peracetic acid has been reported in this article. The radio-chemical purity (RCP) of the labeled compound was over 95% determined by HPLC and TLC. The stability, partition coefficients were also determined. The pharmacological studies of the imaging agent were performed in rats, mice, rabbits and normal monkey. The ligand showed preferable uptake in brain (1 .9%ID/organ in rats and 4.5%ID/organ in mice at 5 min). The ratios of striatum/cerebellum, hippocampus/cerebellum and cortex/cerebellum were 28.9, 3.97 and 4.75 at 6 h in rats, and 8.52, 2.99 and 3.06 at 6h in mice, respectively. In monkey brain imaging the ratios of striatum/frontal cortex (ST/FC) and striatum/occipital cortex (ST/OC) were 5.14 and 5.97 at 4 h, respectively. All of above showed the high affinity of the ligand to DAT. The compound was primarily metabo lized in liver because the hepatic uptake was much higher than other organs (75.4%ID/organ at 18h). The half-life of blood elimination was 5min The dose received by mice was 2500 times as high as that received by human in the test of undue toxicity, which evaluated the safety of the agent. All the results suggest that fl-CIT can be used as a potential DAT imaging agent.
