Lundgren G, Nordgren I, Karlén B, Jacobsson G
Pharmacol Toxicol. 1987 Feb;60(2):96-9. doi: 10.1111/j.1600-0773.1987.tb01503.x.
The effect of diazepam on the acetylcholine (ACh) synthesizing system has been studied in mouse brain in vivo. ACh and choline (Ch) were analyzed by gas chromatography - mass spectrometry using deuterated internal standards. Turnover of ACh was studied by following the incorporation of Ch into ACh after an intravenous injection of [2H6]-Ch. The mice were killed by focussed microwave irradiation on the head. Diazepam was found to increase the endogenous level of Ch, while the concentration of [2H6]-Ch was only half of that of the controls. The incorporation of [2H6]-Ch into [2H6]-ACh was decreased, while the endogenous level of ACh was slightly increased. The turnover rate of ACh was decreased, consistent with a decrease in neuronal excitability induced by diazepam. The elevated endogenous Ch-level and the lower concentration of [2H6]-Ch in the brain, might be explained by an effect of diazepam on the Ch-transport across the blood-brain barrier. This theory is supported by experiments where levels of endogenous and [2H6]-labelled Ch were analyzed in blood following an intravenous injection of [2H6]-Ch. The [2H6]-Ch was found to be eliminated faster in blood from diazepam treated mice. The increased blood level of endogenous Ch, induced by the [2H6]-Ch injection also returned more rapidly to normal in these animals. This is consistent with peripheral Ch being eliminated faster when the central Ch supply is decreased.
已在小鼠脑内活体研究了地西泮对乙酰胆碱（ACh）合成系统的影响。使用氘代内标通过气相色谱 - 质谱法分析ACh和胆碱（Ch）。通过静脉注射[2H6]-Ch后追踪Ch掺入ACh的情况来研究ACh的周转率。通过聚焦头部微波辐射处死小鼠。发现地西泮可提高内源性Ch水平，而[2H6]-Ch的浓度仅为对照组的一半。[2H6]-Ch掺入[2H6]-ACh减少，而内源性ACh水平略有增加。ACh的周转率降低，这与地西泮诱导的神经元兴奋性降低一致。脑内升高的内源性Ch水平和较低的[2H6]-Ch浓度，可能是由于地西泮对Ch跨血脑屏障转运的影响所致。静脉注射[2H6]-Ch后分析血液中内源性和[2H6]-标记的Ch水平的实验支持了这一理论。发现[2H6]-Ch在接受地西泮治疗的小鼠血液中消除更快。[2H6]-Ch注射诱导的内源性Ch血液水平升高在这些动物中也更快恢复正常。这与当中央Ch供应减少时外周Ch消除更快一致。
