Zahniser N R, Chou D, Hanin I
J Pharmacol Exp Ther. 1977 Mar;200(3):545-59.
Acute administration of deanol-p-acetamidobenzoate (Deaner; deanol) has been reported to elevate brain choline (CH) and acetylcholine (ACh) levels. We have developed a specific and sensitive gas chromatographic assay to measure deanol levels in tissue and have applied this assay to our studies of the effect of acute deanol administration on deanol, ACh and Ch levels in rodent brains. Details of the method are described in this text. This procedure is quantitative and yields reproducible results over a wide range of deanol concentrations (0.30-200 nmol). Seven endogenous and pharmacological parameters have been studied using this procedure. In control rodent brain, liver, heart, lung and plasma, we detected no free endogenous deanol (less than 1 nmol/g). After deanol administration, we were able to detect deanol in tissue and have attempted to determine a relationship between these levels and values of ACh in the same tissue. Regardless of deanol pretreatment time (1-30 minutes) or doses (33.3-3000 mg/kg i.p.) used, we detected no increase in mouse whole brain ACh levels. Likewise, there was no detectable elevation in ACh levels in rat whole brain, cortex, striatum or hippocampus after a 15-minute pretreatment with 550 mg/kg of deanol (i.p.). The only elevation in ACh levels which we detected occurred selectively in the striatum of mice pretreated with a massive dose (900 mg/kg i.p.) of deanol for 30 minutes. This selective increase in striatal ACh levels oculd not, however, be related to levels of deanol in the striatum because there was no greater accumulation of deanol in the striatum than in other brain areas tested or in whole brain. These data do not confirm the results of other investigators who reported elevations in whole brain or striatal ACh levels after acute administration of lower doses of deanol. The data emphasize the need for further investigation into the mode of action of deanol and question its suggested role as an immediate precursor of ACh synthesis in the central nervous system.
据报道,急性给予对乙酰氨基苯甲酸二乙胺酯(迪阿纳;二乙胺酯)可提高脑胆碱(CH)和乙酰胆碱(ACh)水平。我们已开发出一种特异且灵敏的气相色谱分析法来测量组织中的二乙胺酯水平,并将该分析法应用于我们关于急性给予二乙胺酯对啮齿动物脑内二乙胺酯、ACh 和 CH 水平影响的研究中。本文描述了该方法的详细信息。此程序是定量的,在广泛的二乙胺酯浓度范围(0.30 - 200 nmol)内可产生可重复的结果。已使用该程序研究了七个内源性和药理学参数。在对照啮齿动物的脑、肝、心、肺和血浆中,我们未检测到游离的内源性二乙胺酯(低于 1 nmol/g)。给予二乙胺酯后,我们能够在组织中检测到二乙胺酯,并试图确定这些水平与同一组织中 ACh 值之间的关系。无论二乙胺酯预处理时间(1 - 30 分钟)或所用剂量(33.3 - 3000 mg/kg 腹腔注射)如何,我们均未检测到小鼠全脑 ACh 水平升高。同样,在用 550 mg/kg 二乙胺酯(腹腔注射)预处理 15 分钟后,大鼠全脑、皮质、纹状体或海马体中的 ACh 水平也未检测到升高。我们检测到的 ACh 水平唯一升高发生在用大剂量(900 mg/kg 腹腔注射)二乙胺酯预处理 30 分钟的小鼠纹状体中。然而,纹状体中 ACh 水平的这种选择性升高与纹状体中二乙胺酯的水平无关,因为纹状体中二乙胺酯的积累并不比其他测试脑区或全脑中更多。这些数据并未证实其他研究者所报道的急性给予较低剂量二乙胺酯后全脑或纹状体 ACh 水平升高的结果。这些数据强调需要进一步研究二乙胺酯的作用方式,并对其作为中枢神经系统中 ACh 合成的直接前体的假定作用提出质疑。