Perry K W, Fuller R W
Lilly Research Laboratories, Eli Lilly & Co., Indianapolis, IN 46285.
Biochem Pharmacol. 1989 Oct 1;38(19):3169-73. doi: 10.1016/0006-2952(89)90609-6.
A liquid chromatographic method using electrochemical detection is described for the assay of brain concentrations of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), centrally acting serotonin agonists selective for the 5HT-1A subtype of serotonin receptors. The method is sensitive to approximately 5 ng/g concentrations. After a 1mg/kg s.c. dose of 8-OH-DPAT in rats, its concentration in whole brain declined rapidly during the first 4 hr with a half-life of 26 min. At 30 min after a 1 mg/kg s.c. dose of 8-OH-DPAT, concentrations were approximately equal in hypothalamus, striatum, hippocampus, cerebellum and brain stem but were slightly lower in midbrain. 8-OH-DPAT disappeared from hypothalamus, midbrain and hippocampus at similar rates during the first 90 min after a 1 mg/kg s.c dose. Concentrations of 8-OH-DPAT in whole brain were markedly higher after s.c. than after i.p. administration of 8-OH-DPAT, consistent with earlier data showing 8-OH-DPAT to be more potent when given s.c. than when given i.p. in decreasing brain concentrations of 5-hydroxyindoleacetic acid. Pretreatment with proadifen (SKF-525A), an inhibitor of microsomal drug metabolism, slightly increased brain concentrations of 8-OH-DPAT. Pindolol, which antagonized the elevation of serum corticosterone concentration by 8-OH-DPAT, did not alter brain concentrations of 8-OH-DPAT. The analytical method should be useful in correlating brain concentrations of 8-OH-DPAT with various neurochemical, behavioral or other functional effects that have been described for this compound.
本文描述了一种采用电化学检测的液相色谱法，用于测定脑内8-羟基-2-（二正丙基氨基）四氢萘（8-OH-DPAT）的浓度，8-OH-DPAT是一种对5-羟色胺受体5HT-1A亚型具有选择性的中枢作用5-羟色胺激动剂。该方法对大约5 ng/g的浓度敏感。大鼠皮下注射1mg/kg剂量的8-OH-DPAT后，其在全脑的浓度在最初4小时内迅速下降，半衰期为26分钟。皮下注射1mg/kg剂量的8-OH-DPAT后30分钟，下丘脑、纹状体、海马体、小脑和脑干中的浓度大致相等，但中脑中的浓度略低。皮下注射1mg/kg剂量的8-OH-DPAT后，在最初90分钟内，8-OH-DPAT在下丘脑、中脑和海马体中的消失速率相似。皮下注射8-OH-DPAT后全脑中8-OH-DPAT的浓度明显高于腹腔注射后，这与早期数据一致，即皮下注射8-OH-DPAT在降低脑内5-羟吲哚乙酸浓度方面比腹腔注射更有效。用微粒体药物代谢抑制剂丙胺太林（SKF-525A）预处理可使脑内8-OH-DPAT的浓度略有增加。普萘洛尔可拮抗8-OH-DPAT引起的血清皮质酮浓度升高，但不改变脑内8-OH-DPAT的浓度。该分析方法有助于将8-OH-DPAT的脑内浓度与已描述的该化合物的各种神经化学、行为或其他功能效应联系起来。
