Pharmacodynamics of ziprasidone in children and adolescents: impact on dopamine transmission.
Pharmacodynamics of ziprasidone in children and adolescents: impact on dopamine transmission.
复制标题
齐拉西酮在儿童和青少年中的药效学：对多巴胺传递的影响。
DOI：
10.1097/01.chi.0000046897.27264.46
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Wilner,Keith
中科院分区：
文献类型：
--
作者：
Sallee,FloydR;Gilbert,DonaldL;Vinks,AlexanderA;Miceli,JeffreyJ;Robarge,Lisa;Wilner,Keith
齐拉西酮是一种非典型抗精神病药，具有高比例的5-HT 2A与D2受体拮抗作用。它也是5-HT 1A的激动剂，已在大鼠中显示出增加前额皮质中的多巴胺。本研究的目的是探讨齐拉西酮的多巴胺激动剂和拮抗剂的药效学特性在youth.METHODA单剂量，开放标签研究进行了24名青年，7至16岁，与抽动秽语综合征或慢性抽动障碍。给予齐拉西酮口服混悬液（40 mg/mL）以达到0.2 - 0.3 mg/kg。随后评估患者的血清齐拉西酮、血清催乳素和眨眼率。催乳素（基线平均值7.2 ng/mL，95%置信区间[CI] 5.2-9.2）在4小时达到峰值（平均值27.5 ng/mL，95% CI 22.6-32.3）。每5分钟的眨眼率（基线平均值60，95%CI 42-79）在6小时达到峰值（平均值74，95%CI 52-96）。结论齐拉西酮急性阻断多巴胺传递，如催乳素水平增加所示，并以延迟的方式，似乎刺激多巴胺能传递，如自发眨眼增加所示。多巴胺能刺激的机制被认为是间接的，通过5-HT 1A激动作用。
OBJECTIVEZiprasidone is an atypical antipsychotic with a high ratio of 5-HT2Ato D2receptor antagonism. It is also an agonist at 5-HT1A, which has been shown in rats to increase dopamine in prefrontal cortex. The objective of this study was to probe the dopamine agonist and antagonist pharmacodynamic properties of ziprasidone in youth.METHODA single-dose, open-label study was conducted in 24 youths, 7 to 16 years of age, with Tourette syndrome or chronic tic disorder. Ziprasidone oral suspension (40 mg/mL) was given to achieve 0.2 to 0.3 mg/kg. Patients were subsequently assessed for serum ziprasidone, serum prolactin, and eye blink rates.RESULTSSerum ziprasidone peaked 4 hours postdose. Prolactin (baseline mean 7.2 ng/mL, 95% confidence interval [CI] 5.2–9.2) peaked at 4 hours (mean 27.5 ng/mL, 95% CI 22.6–32.3). Eyeblink rates per 5 minutes (baseline mean 60, 95% CI 42–79) peaked at 6 hours (mean 74, 95% CI 52–96).CONCLUSIONSZiprasidone acutely blocks dopamine transmission, as indicated by increased prolactin levels, and, in a delayed fashion, appears to stimulate dopaminergic transmission, as indicated by the increase in spontaneous eye blinks. The mechanism of dopaminergic stimulation is presumed to be indirect, via 5-HT1Aagonism.