A novel synthesis and pharmacological evaluation of a potential dopamine D1/D2 agonist: 1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinoline-6,7-diol.

Previously, we have demonstrated that enone prodrugs of dopaminergic catecholamines represent a new type of dopamine (DA) agonist. Trans-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinoline-6,7-diol (TL-334), the active form of trans-1-propyl-2,3,4,4a,5,7,8,9,10,10a-decahydro-1H-benzo[g]quinolin-6-one (GMC-6650), in vivo showed an extremely potent dopaminergic activity. Here, we report a novel synthesis and a pharmacological evaluation of TL-334 by means of microdialysis.

Extremely potent orally active benzo[g]quinoline analogue of the dopaminergic prodrug: 1-propyl-trans-2,3,4,4a,5,7,8,9,10,10a-decahydro-1H-benzo-[g]quinolin-6-one [corrected].

Enone prodrugs of dopaminergic catecholamines represent a new type of prodrug in the research area of dopamine agonists. Here, we demonstrate the first benzo[g]quinoline-derived enone that induces potent dopamine agonist effects similar to aminotetralin-derived enones. Significant effects of (-)-4 were observed in microdialysis studies after administration of 1 nmol kg(-1) sc and 3 nmol kg(-1) po.

Evidence for activation of histamine H3 autoreceptors during handling stress in the prefrontal cortex of the rat.

On-line microdialysis of histamine in 10-min samples of the prefrontal cortex of the conscious rat is described. The HPLC-fluorescent assay for histamine in dialysates has been significantly simplified by using only one postcolumn reagent line instead of the three reagent lines described in earlier methods. The method is selective, sensitive (detection limit: 2-3 fmol on column), and linear over a large concentration range.