Baumgold J, Abood L G, Aronstam R
Brain Res. 1977 Mar 25;124(2):331-40. doi: 10.1016/0006-8993(77)90889-7.
A study was undertaken of the possible relationship of the binding affinity of a series of anticholinergic psychotomimetic drugs to their psychopharmacological and anticholinergic effects. Binding was measured to brain homogenates and nerve endings using [3H]quinuclidinyl benzilate (QB), a highly potent psychotomimetic agent presumably affecting muscarinic sites in the brain. The two stereoisomers of QB were compared; and although the L-isomer had 15 times the binding affinity of D-isomer, the L-isomer had over 200 times the psychopharmacological potency of the D-form. When the relative binding affinity of a homologous series of glycolate esters was compared with their relative psychoacitve potency, the correlation was excellent; however, when compounds with heterocyclic amino rings (e.g., tropanol) other than quinuclidine and piperidine were considered, the correlation was poor. The correlation between binding affinity and antagonism to acetylcholine-induced contraction of ileum was more consistent. A study was undertaken on the effect of added lipids on QB binding to nerve endings, and it was found that phosphatidyl serine had a significant enhancing effect while gangliosides were inhibitory.
对一系列抗胆碱能拟精神病药物的结合亲和力与其精神药理作用和抗胆碱能作用之间的可能关系进行了研究。使用[3H]喹核醇基苯甲酸酯（QB）测定其与脑匀浆和神经末梢的结合，QB是一种高效的拟精神病药物，可能作用于脑中的毒蕈碱位点。比较了QB的两种立体异构体；虽然L-异构体的结合亲和力是D-异构体的15倍，但L-异构体的精神药理效力是D-型的200多倍。当比较一系列乙醇酸酯的相对结合亲和力与其相对精神活性效力时，相关性极佳；然而，当考虑除喹核碱和哌啶之外带有杂环氨基环（如托烷醇）的化合物时，相关性较差。结合亲和力与对乙酰胆碱诱导的回肠收缩的拮抗作用之间的相关性更为一致。研究了添加脂质对QB与神经末梢结合的影响，发现磷脂酰丝氨酸有显著增强作用，而神经节苷脂则有抑制作用。
