Karlsson P, Farde L, Halldin C, Sedvall G, Ynddal L, Sloth-Nielsen M
Department of Clinical Neuroscience, Karolinska Hospital, Stockholm, Sweden.
Psychopharmacology (Berl). 1995 May;119(1):1-8. doi: 10.1007/BF02246046.
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-dopamine 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 Ki value 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.
NNC 756是一种对D1-多巴胺受体具有高亲和力和选择性的新型苯并氮杂卓类药物。在一项双盲、安慰剂对照的交叉研究中，利用正电子发射断层扫描技术和放射性配体[11C]SCH 23390，在三名健康男性单次口服80 mg NNC 756后，测定中枢D1-多巴胺受体占有率。给药后1.5小时，NNC 756在壳核中诱导的D1-多巴胺受体占有率分别为75%、66%和47%，7.5小时后分别为46%、36%和24%。占有率值与血清浓度之间呈双曲线关系。该双曲线的Ki值为6.4 ng/ml（±标准差1.4）。1.5小时时的占有率与动物模型中显示出可预测抗精神病作用的诱导效应处于同一水平。在血清药物浓度峰值时，两名受试者出现坐立不安（静坐不能），一名受试者出现恶心。80 mg的口服剂量水平应适合用于研究NNC 756的潜在抗精神病作用。
