N-substituted octahydro-4a-(3-hydroxyphenyl)-10a-methyl-benzo[g]isoquinolines are opioid receptor pure antagonists.
N-Methyl- and N-phenylethyl-(+/-)-1,2,3,4,4a,5,10,10a- octahydro-4a-(3-hydroxyphenyl)-10a-methyl-benzo[g]isoquinolines (4 and 5, respectively) were found to be pure opioid antagonists. These compounds were shown to share many of the characteristics identified with the N-methyl- and N-phenylethyl trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidine (1 and 2, respectively) including N-substituent mediated potency and a lack of N-substituent mediated antagonism. These data suggest that compounds 4 and 5 and the N-substituted trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidines (1 and 2) may interact with opioid receptors similarly.
Thomas
J B
JB
Chemistry and Life Sciences, Research Triangle Institute, North Carolina 27709, USA.
Mascarella
S W
SW
Burgess
J P
JP
Xu
H
H
McCullough
K B
KB
Rothman
R B
RB
Flippen-Anderson
J L
JL
George
C F
CF
Cantrell
B E
BE
Zimmerman
D M
DM
Carroll
F I
FI
D000818:Animals; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006168:Guinea Pigs; D007546:Isoquinolines / Q000138:chemical synthesis* / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D013329:Structure-Activity Relationship
D007546:Isoquinolines; D009292:Narcotic Antagonists; D010880:Piperidines; D016244:Guanosine 5'-O-(3-Thiotriphosphate)