Rodda Kabrena E, Dean Brian, McIntyre Iain M, Drummer Olaf H
Victorian Institute of Forensic Medicine, Department of Forensic Medicine, Monash University, 57-83 Kavanagh Street, Southbank, Vic. 3006, Australia.
Forensic Sci Int. 2006 Mar 10;157(2-3):121-30. doi: 10.1016/j.forsciint.2005.03.017. Epub 2005 Jun 4.
The brain distribution of phenothiazine antipsychotics in 22 confirmed schizophrenic and 11 control subjects were collected at autopsy. Specimens were homogenized, extracted with n-butyl chloride, and analyzed via liquid chromatography-mass spectrometry, using atmospheric pressure electrospray ionization operating in the positive mode. Drug concentrations normalized for those observed in cerebellum showed three distinct patterns of distribution corresponding to different structural features of each type of phenothiazine. Those drugs with high affinity for dopamine receptors were detected in the highest concentrations in regions with high concentrations of such receptors. However, those associated with relatively lower dopaminergic activity were found in the highest concentration in the occipital cortex, a region with a relatively low concentration of dopamine receptors. The regional brain distribution of thioridazine and its metabolites was concentration dependent. These results have implications for determining the role of these drugs in the sudden and unexpected deaths of schizophrenics.
在尸检时收集了22名确诊精神分裂症患者和11名对照受试者中吩噻嗪类抗精神病药物的脑部分布情况。将标本匀浆，用正丁基氯萃取，并通过液相色谱 - 质谱联用仪进行分析，采用正模式运行的大气压电喷雾电离。以小脑观察到的浓度进行归一化处理后的药物浓度显示出三种不同的分布模式，对应于每种吩噻嗪类药物的不同结构特征。对多巴胺受体具有高亲和力的那些药物，在多巴胺受体浓度高的区域中检测到的浓度最高。然而，与多巴胺能活性相对较低相关的那些药物，在枕叶皮质（多巴胺受体浓度相对较低的区域）中浓度最高。硫利达嗪及其代谢产物的脑区分布是浓度依赖性的。这些结果对于确定这些药物在精神分裂症患者突然意外死亡中的作用具有启示意义。
