Hexahydrobenzo[a]phenanthridines: novel dopamine D3 receptor ligands.
We report that certain substituted hexahydrobenzo[a]phenanthridines are novel high affinity ligands selective for the dopamine D3 receptor. These data demonstrate that substitutions on the heterocyclic nitrogen and the pendant phenyl ring of this nucleus cause a marked increase in both affinity and selectivity for dopamine D3 vs. D2 receptors. Thus, these compounds represent important new tools to study the pharmacology of dopamine D3 receptors, and may also provide an opportunity for the synthesis of new radioligands for dopamine D3 receptors.
Watts
V J
VJ
Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill 27599-7250.
Lawler
C P
CP
Knoerzer
T
T
Mayleben
M A
MA
Neve
K A
KA
Nichols
D E
DE
Mailman
R B
RB
D000818:Animals; D001665:Binding Sites; D005910:Glioma; D010617:Phenanthridines / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism*; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D013329:Structure-Activity Relationship; D013764:Tetrahydronaphthalenes / Q000378:metabolism; D014407:Tumor Cells, Cultured
C493595:Drd3 protein, rat; D010617:Phenanthridines; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D013764:Tetrahydronaphthalenes; C083948:4-methyl-N-n-propyldihydrexidine; C031349:7-hydroxy-2-N,N-dipropylaminotetralin