Kanba S, Suzuki E, Nomura S, Nakaki T, Yagi G, Asai M, Richelson E
Department of Neuro-psychiatry, Keio University, School of Medicine, Tokyo, Japan.
J Psychiatry Neurosci. 1994 Jul;19(4):265-9.
We determined the inhibition-dissociation constant (Ki) of a number of neuroleptics for D1 receptors of normal human brain tissue using [3H]SCH23390 [R-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3[benzazepine-7- ol]. SCH23390 had the highest affinity with a Ki of 0.76 nM. Among clinically used drugs, propericiazine showed the highest affinity with a Ki of 10 nM. When neuroleptics were classified according to chemical structures, the Ki values were as follows. Phenothiazines ranged from 10 nM to 250 nM. Butyrophenones ranged from 45 nM to 250 nM. Thioxanthenes ranged from 12 nM to 340 nM. Orthopramines were more than 10,000 nM. The Ki values for the binding site of this study were significantly correlated with those reported in studies using animal brain. The possible relationship between D1 receptors and negative symptoms is discussed.
我们使用[3H]SCH23390[R-(+)-8-氯-2,3,4,5-四氢-3-甲基-5-苯基-1H-3-苯并氮杂卓-7-醇]测定了多种抗精神病药物对正常人类脑组织D1受体的抑制解离常数（Ki）。SCH23390的亲和力最高，Ki为0.76 nM。在临床使用的药物中，丙嗪的亲和力最高，Ki为10 nM。当根据化学结构对抗精神病药物进行分类时，Ki值如下。吩噻嗪类药物的Ki值范围为10 nM至250 nM。丁酰苯类药物的Ki值范围为45 nM至250 nM。硫杂蒽类药物的Ki值范围为12 nM至340 nM。邻苯二胺类药物的Ki值大于10000 nM。本研究中结合位点的Ki值与使用动物脑的研究中报道的Ki值显著相关。文中还讨论了D1受体与阴性症状之间可能的关系。
