Bressan Rodrigo A, Erlandsson Kjell, Spencer Edgar P, Ell Peter J, Pilowsky Lyn S
Section of Neurochemical Imaging, Institute of Psychiatry, King's College London, Denmark Hill, London, UK.
Psychopharmacology (Berl). 2004 Sep;175(3):367-73. doi: 10.1007/s00213-004-1826-6.
Atypical antipsychotic drugs are classically associated with lower propensity to extrapyramidal symptoms (EPS) and hyperprolactinemia than typical antipsychotic drugs. It has not been clarified why some atypical antipsychotic drugs, such as amisulpride, induce prolactin plasma concentration (PRL) elevation, but little EPS. Previous studies have found an association between striatal D2/D3 receptor occupancy and PRL in typical antipsychotic treated patients suggesting that PRL is a marker of central D2/D3 receptors blockade.
We have evaluated the relationship between PRL and central (striatum, temporal cortex and thalamus) D2/D3 receptor occupancy in amisulpride treated schizophrenic patients.
Single photon emission tomography (SPET) and [123I]-epidepride were used to determine D2/D3 receptor occupancy in eight amisulpride treated patients. PRL was measured concurrently with the scans.
The mean PRL was 1166 (range 499-1892 mIU/l) for a mean amisulpride dose of 406 mg/day (range 150-600 mg/day). Amisulpride plasma concentration and central D2/D3 receptor occupancy were positively correlated (r=0.83-0.89, df=4, P<0.05). No significant correlations were observed between PRL and amisulpride (daily dose or plasma concentration, P>0.05), or between PRL and central D2/D3 receptor occupancy (P>0.05).
Our findings show that amisulpride-induced hyperprolactinemia is uncoupled from central D2/D3 receptor occupancy. Amisulpride has poor blood-brain barrier penetration and reaches much higher concentration at the pituitary, which is outside the blood-brain barrier. Higher D2/D3 receptor occupancy at the pituitary gland than at central regions is a possible explanation for amisulpride PRL elevation with low EPS. Further studies evaluating pituitary D2/D3 receptor occupancy in vivo are necessary to confirm this hypothesis.
与典型抗精神病药物相比，非典型抗精神病药物通常导致锥体外系症状（EPS）和高催乳素血症的倾向较低。目前尚不清楚为什么某些非典型抗精神病药物，如氨磺必利，会导致血浆催乳素浓度（PRL）升高，但EPS却很少。先前的研究发现，在接受典型抗精神病药物治疗的患者中，纹状体D2/D3受体占有率与PRL之间存在关联，这表明PRL是中枢D2/D3受体阻断的一个标志物。
我们评估了氨磺必利治疗的精神分裂症患者中PRL与中枢（纹状体、颞叶皮质和丘脑）D2/D3受体占有率之间的关系。
使用单光子发射断层扫描（SPET）和[123I]-表哌立松来测定8例接受氨磺必利治疗患者的D2/D3受体占有率。在扫描的同时测量PRL。
氨磺必利平均日剂量为406mg/天（范围150 - 600mg/天）时，平均PRL为1166（范围499 - 1892mIU/l）。氨磺必利血浆浓度与中枢D2/D3受体占有率呈正相关（r = 0.83 - 0.89，自由度 = 4，P < 0.05）。未观察到PRL与氨磺必利（日剂量或血浆浓度，P > 0.05）之间或PRL与中枢D2/D3受体占有率之间存在显著相关性（P > 0.05）。
我们的研究结果表明，氨磺必利引起的高催乳素血症与中枢D2/D3受体占有率无关。氨磺必利的血脑屏障穿透性较差，在血脑屏障外的垂体处达到更高的浓度。垂体处的D2/D3受体占有率高于中枢区域可能是氨磺必利导致PRL升高且EPS较低的一个解释。有必要进行进一步的体内评估垂体D2/D3受体占有率的研究来证实这一假设。
