Optically pure (-)-4-[(N-allyl-3-methyl-4-piperidinyl)phenyl-amino]-N,N-diethylbenzami de displays selective binding and full agonist activity for the delta opioid receptor.
The optical isomers of 4-[(N-allyl-3-methyl-4-piperidinyl)phenylamino]-N,N-diethylbenzamide+ ++ (3) have been prepared and tested in both binding and functional assays. The data show that (-)-3 is responsible for the delta opioid activity demonstrated by the racemic material. This compound displays a binding affinity of 5.5 nM for the delta opioid receptor as well as a 470-fold delta versus mu selectivity. Importantly, (-)-3 is a full agonist at the delta receptor in comparison with SNC-80 (2). Taken together, the data suggest that (-)-3 behaves more like the prototypical delta agonists, BW373U86 or SNC-80, and less like the peptidomimetic compound SL-3111 (5).
Thomas
J B
JB
Chemistry and Life Sciences, Research Triangle Institute, Research Triangle Park, NC 27709, USA.
Atkinson
R N
RN
Herault
X M
XM
Rothman
R B
RB
Mascarella
S W
SW
Dersch
C M
CM
Xu
H
H
Horel
R B
RB
Carroll
F I
FI
D001549:Benzamides / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D001921:Brain / Q000378:metabolism; D010880:Piperidines / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D011869:Radioligand Assay; D017465:Receptors, Opioid, delta / Q000187:drug effects / Q000378:metabolism*
C401942:4-((N-allyl-3-methyl-4-piperidinyl)phenylamino)-N,N-diethylbenzamide; D001549:Benzamides; D010880:Piperidines; D017465:Receptors, Opioid, delta