Chiueh C C, Zukowska-Grojec Z, Kirk K L, Kopin I J
J Pharmacol Exp Ther. 1983 Jun;225(3):529-33.
In the present study 6-fluoronorepinephrine (6F-NE) is shown to be formed from 6-fluorodopamine (6F-DA) in vivo. The beta-hydroxylated fluorocompound is taken up by and stored in the adrenergic nerve terminals and can be released during sympathetic nerve stimulation. In the heart, the turnover rate of the exogenously administered 6F-NE was about the same as that of tritium-labeled norepinephrine. In the central nervous system, 6F-DA can be taken up by the nigrostriatal neurons. After depolarization of the dopaminergic neurons by potassium, 6F-DA is released along with the endogenous dopamine. Systemic administration of 6F-NE to the pithed rats produces dose-dependent increases in blood pressure but does not increase the heart rate. The vasopressor potency of 6F-NE is about the same as that of l-norepinephrine, about 2-fold greater than that of dl-norepinephrine. Combined treatment with yohimbine and prazosin antagonizes completely the vasopressor effect of 6F-NE. The duration of the pressor response to 6F-NE was twice that of dl- or l-norepinephrine. The present study indicates that 6-fluorocatecholamines fulfill the criteria for adrenergic false transmitters and may be useful in positron emission tomographic scanning for mapping specifically the adrenergic nervous system in the brain or in the peripheral sympathetic nerves.
在本研究中,6-氟去甲肾上腺素(6F-NE)被证明可在体内由6-氟多巴胺(6F-DA)形成。这种β-羟基化的氟化合物被肾上腺素能神经末梢摄取并储存,且在交感神经刺激时可释放。在心脏中,外源性给予的6F-NE的周转速率与氚标记的去甲肾上腺素大致相同。在中枢神经系统中,6F-DA可被黑质纹状体神经元摄取。在用钾使多巴胺能神经元去极化后,6F-DA与内源性多巴胺一同释放。对脊髓被切断的大鼠全身给予6F-NE会使血压呈剂量依赖性升高,但不会使心率增加。6F-NE的升压效力与左旋去甲肾上腺素大致相同,约为消旋去甲肾上腺素的2倍。育亨宾和哌唑嗪联合治疗可完全拮抗6F-NE的升压作用。对6F-NE的升压反应持续时间是消旋或左旋去甲肾上腺素的两倍。本研究表明,6-氟儿茶酚胺符合肾上腺素能假递质的标准,可能有助于正电子发射断层扫描,以专门绘制大脑或外周交感神经中的肾上腺素能神经系统图谱。