Dihydrexidine: a new potent peripheral dopamine D1 receptor agonist.
Dihydrexidine (trans-10,11-dihydroxyhexahydrobenzo-[a]phenanthridine) was found to be a full dopamine D1 receptor agonist with a potency five times that of dopamine. Dihydrexidine showed no agonist activity at peripheral dopamine D2 receptors, alpha- or beta-adrenoceptors at the doses which produced near maximal stimulation of dopamine D1 receptors. The chemical structure of dihydrexidine shows that addition of a phenyl ring to a benzo[f]quinoline moiety bestows potent D1 activity upon a structure which had no such activity previously. This observation introduces a new factor in structure-activity considerations for dopamine receptor ligands.
Kohli
J D
JD
University of Chicago, IL 60637.
Horn
P T
PT
Glock
D
D
Brewster
W K
WK
Nichols
D E
DE
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D004298:Dopamine / Q000494:pharmacology; D015259:Dopamine Agents / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D007668:Kidney / Q000098:blood supply / Q000187:drug effects; D010617:Phenanthridines / Q000494:pharmacology*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D011943:Receptors, Adrenergic, beta / Q000187:drug effects; D017447:Receptors, Dopamine D1 / Q000187:drug effects* / Q000378:metabolism; D012079:Renal Circulation / Q000187:drug effects; D013329:Structure-Activity Relationship; D014655:Vascular Resistance / Q000187:drug effects
D015259:Dopamine Agents; D010617:Phenanthridines; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D017447:Receptors, Dopamine D1; C061532:dihydrexidine; D004298:Dopamine