Freeman J J, Macri J R, Choi R L, Jenden D J
J Pharmacol Exp Ther. 1979 Jul;210(1):91-7.
Hemicholinium (HC-3) causes a behavioral reactivity in rats which is correlated with the depletion of brain acetylcholine (ACh). The decrease in ACh levels and behavioral effects caused by HC-3 are correlated in a dose-dependent manner, maximal effects being achieved at an intraventricular (i.vt.) dose of 1 microgram. The HC-3 concentration in the brain 2 hr after i.vt. injection does not increase further with doses greater than 10 microgram. HC-3 (i.vt.) does not affect the uptake of choline (Ch) into subcellular fractions prepared from treated animals. ACh depletion in the brain areas studied closely parallels the HC-3 distribution. HC-3 pretreatment results in greater effects on newly synthesized than on stored ACh. Utilizing a concentration equal to that found in brain after an in vivo dose, HC-3 does not inhibit the uptake of Ch in synaptosomal preparations in which the neuronal membrane was disrupted with ether. The commonly accepted mechanism of action of HC-3, i.e., an inhibition of high affinity Ch uptake at the cholinergic nerve terminal, appears to provide a satisfactory explanation of its effects in vivo.
半胆碱（HC - 3）可使大鼠产生行为反应，这种反应与脑内乙酰胆碱（ACh）的耗竭相关。HC - 3引起的ACh水平降低和行为效应呈剂量依赖性相关，脑室内（i.vt.）注射1微克剂量时可达到最大效应。脑室内注射后2小时，剂量大于10微克时，脑内HC - 3浓度不再进一步升高。脑室内注射HC - 3不影响从处理过的动物制备的亚细胞组分对胆碱（Ch）的摄取。所研究脑区的ACh耗竭与HC - 3分布密切平行。HC - 3预处理对新合成的ACh的影响比对储存的ACh的影响更大。使用与体内给药后在脑中发现的浓度相等的HC - 3，在突触体制备物中，HC - 3不抑制用乙醚破坏神经元膜后的Ch摄取。HC - 3通常被接受的作用机制，即抑制胆碱能神经末梢对高亲和力Ch的摄取，似乎为其体内效应提供了令人满意的解释。
