Oral administration of NNC 756--a placebo controlled PET study of D1-dopamine receptor occupancy and pharmacodynamics in man.
Oral administration of NNC 756--a placebo controlled PET study of D1-dopamine receptor occupancy and pharmacodynamics in man.
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口服 NNC 756——一项针对人体 D1-多巴胺受体占据和药效学的安慰剂对照 PET 研究。
DOI：
10.1007/bf02246046
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发表时间：
1995
影响因子：
3.4
通讯作者：
Sloth-Nielsen,M
中科院分区：
文献类型：
--
作者：
Karlsson,P;Farde,L;Halldin,C;Sedvall,G;Ynddal,L;Sloth-Nielsen,M
NNC756是一种新型苯扎西平，对D_1-多巴胺受体具有高亲和力和选择性。在一项双盲、安慰剂对照、交叉研究中，正电子发射断层扫描和放射性配基[11C]SCH 23390被用来确定三名健康男性单次口服80 mg NNC756后的中枢D1-DO-PAME受体占有率。NNC756在给药后1.5h和7.5h分别诱导壳核D1多巴胺受体的75%、66%和47%的占有率和46%、36%和24%的占有率，并与血药浓度呈双曲线关系。双曲线的Ki值为6.4 ng/ml(±SD 1.4)。1.5h的占有率与在动物模型中预测抗精神病药物的诱导效应的水平相同。在血药浓度达到峰值时，2名受试者出现躁动(静坐不能)，1名受试者出现恶心。研究NNC756的潜在抗精神病作用应以80 mg的口服剂量水平为宜。
NNC 756 is a new benzazepine with high affinity and selectivity for D1-dopamine receptors. In a double-blind, placebo controlled, cross-over study, positron emission tomography and the radioligand [11C]SCH 23390 were used to determine central D1-do-pamine receptor occupancy after a single oral dose of 80 mg NNC 756 in three healthy men. NNC 756 induced 75, 66 and 47% occupancy of D1-dopamine receptors in the putamen of at 1.5 h after drug administration and 46, 36 and 24% after 7.5 h. There was a hyperbolic relationship between the occupancy values and the serum concentrations. The Kivalue for the hyperbola was 6.4 ng/ml (±SD 1.4). The occupancy at 1.5 h is on the same level as that shown to induce effects in animal models for prediction of antipsychotic effect. Restlessness (akathisia) appeared in two subjects and nausea in one subject at time of peak drug concentration in serum. The oral dose level of 80 mg should be appropriate to investigate the potential antipsychotic effect of NNC 756.