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. With a potency comparable to that of the most potent apomorphines, (-)-4 could potentially compete with L-DOPA and apomorphine in the treatment of Parkinson's disease.
Department of Medicinal Chemistry, University Centre for Pharmacy, University of Groningen, Antonius Deusinglaan 1, NL-9713 AV Groningen, The Netherlands. d.liu@rug.nl
Danyang
D
Liu
Håkan V
HV
Wikström
Durk
D
Dijkstra
Jan B
JB
de Vries
Bastiaan J
BJ
Venhuis
D015081:2-Naphthylamine / Q000031:analogs & derivatives* / Q000737:chemistry; D000284:Administration, Oral; D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism; D018360:Crystallography, X-Ray; D018491:Dopamine Agonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D066298:In Vitro Techniques; D017551:Microdialysis; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015363:Quinolones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D017447:Receptors, Dopamine D1 / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D050637:Receptors, Dopamine D3 / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
C509276:1-propyl-2,3,4,4a,5,7,8,9,10,10a-decahydro-1H-benzo(g)quinolin-6-one; D018491:Dopamine Agonists; C457999:PD 148903; D011355:Prodrugs; D011804:Quinolines; D015363:Quinolones; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D015081:2-Naphthylamine