A positron emission tomography study of quetiapine in schizophrenia: A preliminary finding of an antipsychotic effect with only transiently high dopamine D2 receptor occupancy
A positron emission tomography study of quetiapine in schizophrenia: A preliminary finding of an antipsychotic effect with only transiently high dopamine D2 receptor occupancy
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DOI：
10.1001/archpsyc.57.6.553
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发表时间：
2000-06-01
影响因子：
--
通讯作者：
Seeman, Philip
中科院分区：
文献类型：
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作者：
Kapur, Shitij;Zipursky, Robert;Seeman, Philip
背景：奎替利是一种新型非典型抗精神病药物。因此，关于其在多巴胺2型（D2）和5-羟色胺2a型（5-HT 2a）受体系统的体内作用的报道相对较少。进行了以下研究，以探索临床剂量范围内的这些影响，并将此信息与其临床特征相关联。方法：12例精神分裂症患者随机分为150 ~ 600 mg/d（n=3，150，300，450和600 mg/d）剂量的奎替鲁胺。治疗3周后，在末次给药后12至14小时，使用正电子发射断层扫描（PET）成像测量D2和5-HT 2a占用率。在基线、PET扫描时和12周时获得临床疗效和不良反应评级。另外2例患者在末次给药后2 - 3小时检查药物的作用。结果：奎替利是一种有效的抗精神病药，可改善基线时的锥体外系症状和催乳素水平升高。在末次给药后12小时达到这些结果，D2占用率最低（0%-27%）。对其他受试者的研究显示，单次给药后2至3小时，奎替鲁确实会引起短暂的高D2占用率（58%-64%），然后在12小时内降至最低水平。结论：奎替鲁肽显示短暂的高D2占用率，在给药间隔结束时降至非常低的水平。Quetidine的低D2占用率可以解释其锥体外系症状和催乳素水平升高的自由。数据表明，短暂的D2占用可能足以产生抗精神病作用。未来的研究控制非药理学作用以及对其他受体的活动将是必要的，以证实这一建议。
Background: Quetiapine is a new atypical antipsychotic medication. As such, relatively little has been published regarding its in vivo effects at the dopamine type 2 (D2) and serotonin type 2a (5-HT2a) receptor systems. The following study was undertaken to explore these effects across the clinical dose range and relate this information to its clinical profile. Methods: Twelve patients with schizophrenia were randomly assigned to doses of 150 to 600 mg/d (n=3, at 150, 300, 450, and 600 mg/d) of quetiapine. After 3 weeks of treatment, D2 and 5-HT2a occupancy were measured using positron emission tomography (PET) imaging, 12 to 14 hours after the last dose. Clinical efficacy and adverse effect ratings were obtained at baseline, at the time of PET scanning, and at 12 weeks. Two additional patients were included to examine the effects of the drug 2 to 3 hours after last dose. Results: Quetiapine was an effective antipsychotic and improved the extrapyramidal symptoms and prolactin level elevation noted at baseline. It achieved these results with minimal (0%-27%) D2 occupancy 12 hours after the last dose. Study of the additional subjects revealed that quetiapine does give rise to transiently high (58%-64%) D2 occupancy 2 to 3 hours after a single dose that then decreases to minimal levels in 12 hours. Conclusions: Quetiapine shows a transiently high D2 occupancy, which decreases to very low levels by the end of the dosing interval. Quetiapine's low D2 occupancy can explain its freedom from extrapyramidal symptoms and prolactin level elevation. The data suggest that transient D2 occupancy may be sufficient for its antipsychotic effect. Future studies controlling for nonpharmacological effects as well as activities on other receptors will be necessary to confirm this suggestion.