Hodé Y, Reimold M, Demazières A, Reischl G, Bayle F, Nuss P, Hameg A, Dib M, Macher J P
FORENAP Research Institute For Neuroscience, Pharmacology and Psychiatry, 68250 Rouffach, France.
Psychopharmacology (Berl). 2005 Jul;180(2):377-84. doi: 10.1007/s00213-005-2172-z. Epub 2005 Mar 15.
Cyamemazine (Tercian) is an antipsychotic drug with anxiolytic properties. Recently, an in vitro study showed that cyamemazine possesses high affinity for serotonin 5-HT(2A) receptors, which was fourfold higher than its affinity for dopamine D(2) receptors (Hameg et al. 2003).
The aim of this study is to confirm these previous data in vivo in patients treated with clinically relevant doses of Tercian.
Eight patients received 37.5, 75, 150 or 300 mg/day of Tercian depending on their symptomatology. Dopamine D(2) and serotonin 5-HT(2A) receptor occupancies (RO) were assessed at steady-state plasma levels of cyamemazine with positron emission tomography (PET), using [(11)C]raclopride and [(11)C]N-methyl-spiperone, respectively. The effective plasma level of the drug leading to 50% of receptor occupancy was estimated by fitting RO with plasma levels of cyamemazine at the time of the PET scan.
Cyamemazine induced near saturation of 5-HT(2A) receptors (RO=62.1-98.2%) in the frontal cortex even at low plasma levels of the drug. On the contrary, occupancy of striatal D(2) receptors increased with plasma levels, and no saturation was obtained even at high plasma levels (RO=25.2-74.9%). The effective plasma level of cyamemazine leading to 50% of D(2) receptor occupancy was fourfold higher than that for 5-HT(2A) receptors. Accordingly, individual 5-HT(2A)/D(2) RO ratios ranged from 1.26 to 2.68. No patients presented relevant increased prolactin levels, and only mild extrapyramidal side effects were noticed on Simpson and Angus Scale.
This in vivo binding study conducted in patients confirms previous in vitro findings indicating that cyamemazine has a higher affinity for serotonin 5-HT(2A) receptors compared to dopamine D(2) receptors. In the dose range 37.5-300 mg, levels of dopamine D(2) occupancy remained below the level for motor side effects observed with typical antipsychotics and is likely to explain the low propensity of the drug to induce extrapyramidal side effects.
氰美马嗪（Tercian）是一种具有抗焦虑特性的抗精神病药物。最近，一项体外研究表明，氰美马嗪对5-羟色胺5-HT(2A)受体具有高亲和力，这一亲和力比其对多巴胺D(2)受体的亲和力高四倍（哈梅格等人，2003年）。
本研究的目的是在接受临床相关剂量Tercian治疗的患者体内证实这些先前的数据。
八名患者根据其症状接受37.5、75、150或300毫克/天的Tercian治疗。使用[（11）C]雷氯必利和[（11）C]N-甲基螺哌隆，通过正电子发射断层扫描（PET）在氰美马嗪的稳态血浆水平下评估多巴胺D(2)和5-羟色胺5-HT(2A)受体占有率（RO）。通过将PET扫描时的RO与氰美马嗪的血浆水平进行拟合，估计导致50%受体占有率的药物有效血浆水平。
即使在药物血浆水平较低时，氰美马嗪也能使额叶皮质中的5-HT(2A)受体接近饱和（RO=62.1-98.2%）。相反，纹状体D(2)受体占有率随血浆水平增加，即使在高血浆水平时也未达到饱和（RO=25.2-74.9%）。导致50%D(2)受体占有率的氰美马嗪有效血浆水平比导致5-HT(2A)受体占有率的有效血浆水平高四倍。因此，个体5-HT(2A)/D(2)RO比率在1.26至2.68之间。没有患者出现相关的催乳素水平升高，在辛普森和安格斯量表上仅观察到轻微的锥体外系副作用。
在患者中进行的这项体内结合研究证实了先前的体外研究结果，表明与多巴胺D(2)受体相比，氰美马嗪对5-羟色胺5-HT(2A)受体具有更高的亲和力。在37.5-300毫克的剂量范围内，多巴胺D(2)占有率水平仍低于使用典型抗精神病药物观察到的运动副作用水平，并可能解释了该药物诱导锥体外系副作用的倾向较低。
