Specific dopamine D-1 and DA1 properties of 4-(mono- and -dihydroxyphenyl)-1,2,3,4-tetrahydroisoquinoline and its tetrahydrothieno[2,3-c]pyridine analogue.
The title compounds were prepared and examined to elucidate further the structure-activity relationships of dopamine agonists related to nomifensine. Two of the compounds, 4-(3,4-dihydroxyphenyl)-1,2,3,4-tetrahydroisoquinoline and 4-(3,4-dihydroxyphenyl)-1,2,3,4-tetrahydrothieno[2,3-c]pyridine, have been reported in the patent literature. In stimulation of rat retinal adenylate cyclase, a measure of dopamine D-1 agonist activity, the tetrahydroisoquinoline was about equipotent to dopamine. The thienyl isostere had nearly twice the potency. Both compounds were potent vasodilators in the canine renal artery, producing dilation through stimulation of DA1 type peripheral dopamine receptors. A monohydroxy analogue, 4-(3-hydroxyphenyl)-1,2,3,4-tetrahydroisoquinoline, had only slight activity in the cyclase assay and was inactive in the canine renal artery. These results, combined with those from an earlier study, demonstrate that N-alkylation decreases both dopamine D-1 and DA-1 agonist potency, with activity ordered as H greater than methyl greater than ethyl greater than propyl. The results also demonstrate the necessity for the catechol function in this series.
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D004285:Dogs; D004298:Dopamine / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology*; D008297:Male; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology*; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D012077:Renal Artery / Q000502:physiology; D012160:Retina / Q000201:enzymology; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects
D007546:Isoquinolines; D011725:Pyridines; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D013876:Thiophenes; D000262:Adenylyl Cyclases; D004298:Dopamine