R(-)2-fluoro-N-n-propylnorapomorphine: a very potent and D2-selective dopamine agonist.
A series of 2-substituted N-n-propylnorapomorphine (NPA) derivatives were synthesized and compared with other DA agonists for affinity to D1 and D2 dopamine (DA) receptors in rat brain corpus striatum tissue. The 2-substituents tested reduced D1 affinity similarly, but enhanced D2 affinity in the rank order: F greater than OH greater than Br greater than OCH3 greater than H greater than or equal to NH2. The extraordinarily high D2 affinity (Ki = 12 pM) and D2 vs. D1 selectivity (57,500) of 2-F-NPA far-exceeded that of all other DA agonists tested, and it was about 10-times more potent than NPA in vivo.
Baldessarini
R J
RJ
Section of Medicinal Chemistry, College of Pharmacy and Allied Health Professions, Northeastern University, Boston, MA 02115.
Kula
N S
NS
Gao
Y
Y
Campbell
A
A
Neumeyer
J L
JL
D000818:Animals; D001058:Apomorphine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism*; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D013329:Structure-Activity Relationship
D015259:Dopamine Agents; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; C066610:2-fluoro-N-n-propylnorapomorphine; D001058:Apomorphine