Graham J H, Maher J R, Robinson S E
Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond, USA.
J Pharmacol Exp Ther. 1995 Aug;274(2):707-17.
The effects of cocaine on dopaminergic function in the rat were compared with those of other local anesthetics having an esteratic linkage (dimethocaine, procaine) or an amide linkage (lidocaine). By means of reverse-phase HPLC with electrochemical detection and gas chromatography-mass spectrometry, levels of dopamine (DA) and its metabolites 3-methoxytyramine (3-MT) and dihydroxyphenylacetic acid were quantified in the striatum, nucleus accumbens and prefrontal cortex after i.p. injection of the drugs or saline. Time course and dose response studies determined the effects of the drugs on these parameters of dopaminergic function. These studies provide strong evidence that the three esteratic local anesthetics cocaine, dimethocaine and procaine all increase the synaptic presence of DA, as reflected in increased levels of 3-MT and the ratio of 3-MT to DA, in the striatum, nucleus accumbens and prefrontal cortex. Surprisingly, procaine had an equal or greater effect than cocaine and dimethocaine on 3-MT levels and the ratio 3-MT/DA. The effects of these drugs on dihydroxyphenylacetic acid, an indicator of intraneuronal metabolism of DA, were more variable. However, the amidergic local anesthetic lidocaine did not affect DA metabolism. Although the exact mechanisms behind the dopaminergic activities of procaine and dimethocaine remain unknown, it is clear that these drugs, as well as cocaine, activate dopaminergic systems in the intact animal.
将可卡因对大鼠多巴胺能功能的影响与其他具有酯键（地美卡因、普鲁卡因）或酰胺键（利多卡因）的局部麻醉剂的影响进行了比较。通过反相高效液相色谱-电化学检测和气相色谱-质谱联用技术，在腹腔注射药物或生理盐水后，对纹状体、伏隔核和前额叶皮质中的多巴胺（DA）及其代谢产物3-甲氧基酪胺（3-MT）和二羟基苯乙酸的水平进行了定量分析。时间进程和剂量反应研究确定了这些药物对多巴胺能功能这些参数的影响。这些研究提供了有力证据，表明三种酯类局部麻醉剂可卡因、地美卡因和普鲁卡因均增加了DA在突触中的含量，这反映在纹状体、伏隔核和前额叶皮质中3-MT水平的升高以及3-MT与DA的比值升高。令人惊讶的是，普鲁卡因对3-MT水平和3-MT/DA比值的影响与可卡因和地美卡因相当或更大。这些药物对二羟基苯乙酸（DA神经元内代谢的指标）的影响更具变异性。然而，酰胺类局部麻醉剂利多卡因不影响DA代谢。尽管普鲁卡因和地美卡因多巴胺能活性背后的确切机制尚不清楚，但很明显，这些药物以及可卡因在完整动物中激活了多巴胺能系统。
