Giorgi O, Corda M G, Biggio G
Department of Experimental Biology, University of Cagliari, Italy.
Eur J Pharmacol. 1988 Oct 26;156(1):71-5. doi: 10.1016/0014-2999(88)90148-3.
The effects of Ro 15-4513, FG 7142 and beta-CCM on the activity of the mesocortical dopaminergic system were examined by measuring the changes in the content of the principal dopamine (DA) metabolite, dihydroxyphenylacetic acid (DOPAC) in the prefrontal cortex of the rat. Ro 15-4513 increased the DOPAC content in the prefrontal cortex in a dose-dependent manner (5-40 mg/kg i.p.) but had no effect on DA concentrations. A similar increase in DOPAC content was induced by FG 7142 (40 mg/kg i.p.) and beta-CCM (8 mg/kg s.c.), two beta-carboline derivatives that interact with benzodiazepine recognition sites as partial inverse agonists. These effects of Ro 15-4513, FG 7142 and beta-CCM on DA metabolism in the prefrontal cortex are mediated via benzodiazepine recognition sites, since they were prevented by the administration of the benzodiazepine antagonists Ro 15-1788 and ZK 93426. These data indicate that Ro 15-4513 is an inverse agonist at benzodiazepine recognition sites.
通过测量大鼠前额叶皮质中主要多巴胺（DA）代谢产物二羟基苯乙酸（DOPAC）含量的变化，研究了Ro 15 - 4513、FG 7142和β-CCM对中脑皮质多巴胺能系统活性的影响。Ro 15 - 4513以剂量依赖性方式（腹腔注射5 - 40 mg/kg）增加前额叶皮质中的DOPAC含量，但对DA浓度无影响。FG 7142（腹腔注射40 mg/kg）和β-CCM（皮下注射8 mg/kg）这两种作为部分反向激动剂与苯二氮䓬识别位点相互作用的β-咔啉衍生物，也诱导了类似的DOPAC含量增加。Ro 15 - 4513、FG 7142和β-CCM对前额叶皮质中DA代谢的这些作用是通过苯二氮䓬识别位点介导的，因为苯二氮䓬拮抗剂Ro 15 - 1788和ZK 93426的给药可阻止这些作用。这些数据表明Ro 15 - 4513是苯二氮䓬识别位点的反向激动剂。
