title: N-substituted octahydro-4a-(3-hydroxyphenyl)-10a-methyl-benzo[g]isoquinolines are opioid receptor pure antagonists.
abstract: 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.
authors.affiliation: Chemistry and Life Sciences, Research Triangle Institute, North Carolina 27709, USA.
authors.forename: J B
authors.initials: JB
authors.lastname: Thomas
authors.forename: S W
authors.initials: SW
authors.lastname: Mascarella
authors.forename: J P
authors.initials: JP
authors.lastname: Burgess
authors.forename: H
authors.initials: H
authors.lastname: Xu
authors.forename: K B
authors.initials: KB
authors.lastname: McCullough
authors.forename: R B
authors.initials: RB
authors.lastname: Rothman
authors.forename: J L
authors.initials: JL
authors.lastname: Flippen-Anderson
authors.forename: C F
authors.initials: CF
authors.lastname: George
authors.forename: B E
authors.initials: BE
authors.lastname: Cantrell
authors.forename: D M
authors.initials: DM
authors.lastname: Zimmerman
authors.forename: F I
authors.initials: FI
authors.lastname: Carroll
mesh_terms: 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
chemical_list: D007546:Isoquinolines; D009292:Narcotic Antagonists; D010880:Piperidines; D016244:Guanosine 5'-O-(3-Thiotriphosphate)