Feenstra M G, Rollema H, Mulder T B, Westerink B H, Horn A S
Life Sci. 1983 Jan 31;32(5):459-65. doi: 10.1016/0024-3205(83)90138-8.
A sensitive and selective method of determination of N,N-dipropylamino-5, 6-dihydroxytetralin and its 6,7-dihydroxy isomer in rat plasma and brain tissue is described. The method is based on isolation of these dopamine receptor agonists from the biological samples on small Sephadex G-10 columns, followed by reversed phase high performance liquid chromatography with amperometric detection. Large volume (2 ml) injections result in on-column sample enrichment without a subsequent loss in column efficiency. Using this method the very low detection limit of 4 pmol/g was achieved in brain tissue. It was found that the lower in vivo potency as a centrally acting dopamine agonist of the 6,7-compared with the 5,6-isomer is almost entirely due to the lower brain concentrations achieved after peripheral administration of equimolar doses. This difference is mainly caused by different rates of O-methylation by catechol-O-methyltransferase, which follows from the fact that inhibition of this enzyme by tropolone leads to almost equal brain concentrations of the two isomers.
本文描述了一种灵敏且具选择性的方法，用于测定大鼠血浆和脑组织中的N,N -二丙基氨基-5,6-二羟基四氢萘及其6,7-二羟基异构体。该方法基于在小型葡聚糖凝胶G - 10柱上从生物样品中分离这些多巴胺受体激动剂，随后进行反相高效液相色谱并采用安培检测法。大体积（2毫升）进样可实现柱上样品富集，且不会导致柱效后续损失。使用该方法在脑组织中实现了4皮摩尔/克的极低检测限。研究发现，与5,6 -异构体相比，6,7 -异构体作为中枢作用多巴胺激动剂的体内效价较低，这几乎完全归因于等摩尔剂量外周给药后在脑中达到的浓度较低。这种差异主要由儿茶酚-O -甲基转移酶的不同O -甲基化速率引起，这一事实源于托酚酮对该酶的抑制导致两种异构体在脑中的浓度几乎相等。
