Frankle W G, Gil R, Hackett E, Mawlawi O, Zea-Ponce Y, Zhu Z, Kochan L D, Cangiano C, Slifstein M, Gorman J M, Laruelle M, Abi-Dargham A
Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY, 10032, USA.
Psychopharmacology (Berl). 2004 Oct;175(4):473-80. doi: 10.1007/s00213-004-1852-4.
To examine the D2 occupancy of two commonly used antipsychotic medications and relate this to the D2 occupancy by endogenous dopamine in schizophrenia.
The aim of this study is to compare the occupancy of striatal D2 receptors by the atypical antipsychotic medications risperidone and olanzapine at fixed dosages and to estimate the effect on D2 occupancy by dopamine as a result of these treatments.
Seven patients with schizophrenia taking risperidone 6 mg/day and nine patients with schizophrenia taking olanzapine 10 mg/day underwent an [123I]IBZM SPECT scan after 3 weeks of treatment. The specific to non-specific equilibrium partition coefficient (V3") after bolus plus constant infusion of the tracer was calculated as [(striatal activity)/(cerebellar activity)]-1. D2 receptor occupancy was calculated by comparing V3" measured in treated patients to an age-corrected V3" value derived from a group of untreated patients with schizophrenia, previously published, according to the following formula: OCC=1-(V3" treated/V3" drug free).
V3" was significantly lower in risperidone treated patients compared with olanzapine treated patients (0.23+/-0.06 versus 0.34+/-0.08, P=-0.01), which translated to a significantly larger occupancy in schizophrenic patients treated with risperidone compared to olanzapine (69+/-8% versus 55 +/-11%, P=0.01). Data from our previous study were used to calculate the occupancy of striatal D2 receptors by antipsychotic medications required to reduce the occupancy of these receptors by endogenous dopamine to control values. In medication-free patients with schizophrenia, the occupancy of striatal D2 receptors by endogenous dopamine is estimated at 15.8%. In healthy controls, the occupancy of striatal D2 receptors by dopamine is estimated at 8.8%. In order to reduce the dopamine occupancy of striatal D2 receptors in patients with schizophrenia to control values, 48% receptor occupancy by antipsychotic medications is required.
These data indicate that the dosage of these medications, found to be effective in the treatment of schizophrenia, reduces DA stimulation of D2 receptors to levels slightly lower than those found in unmedicated healthy subjects.
研究两种常用抗精神病药物的D2受体占有率，并将其与精神分裂症患者内源性多巴胺的D2受体占有率相关联。
本研究旨在比较非典型抗精神病药物利培酮和奥氮平在固定剂量下对纹状体D2受体的占有率，并评估这些治疗对多巴胺D2受体占有率的影响。
7例服用利培酮6mg/天的精神分裂症患者和9例服用奥氮平10mg/天的精神分裂症患者在治疗3周后接受了[123I]IBZM单光子发射计算机断层扫描（SPECT）。在静脉推注加持续输注示踪剂后，计算特异性与非特异性平衡分配系数（V3"），公式为[（纹状体活性）/（小脑活性）]-1。通过将治疗患者中测得的V3"与根据先前发表的一组未治疗精神分裂症患者得出的年龄校正V3"值进行比较，计算D2受体占有率，公式如下：占有率（OCC）=1 - （治疗后的V3"/未用药时的V3"）。
与奥氮平治疗的患者相比，利培酮治疗的患者V3"显著更低（0.23±0.06对0.34±0.08，P = -0.01），这意味着利培酮治疗的精神分裂症患者的受体占有率显著高于奥氮平治疗的患者（69±8%对55±11%，P = 0.01）。利用我们先前研究的数据，计算出将内源性多巴胺对纹状体D2受体的占有率降至对照值所需的抗精神病药物对纹状体D2受体的占有率。在未用药的精神分裂症患者中，内源性多巴胺对纹状体D2受体的占有率估计为15.8%。在健康对照中，多巴胺对纹状体D2受体的占有率估计为8.8%。为了将精神分裂症患者纹状体D2受体的多巴胺占有率降至对照值，抗精神病药物需要占据48%的受体。
这些数据表明，这些被发现对精神分裂症治疗有效的药物剂量，可将多巴胺对D2受体的刺激降低至略低于未用药健康受试者的水平。
