title: Major effect of pyrrolic N-benzylation in norbinaltorphimine, the selective kappa-opioid receptor antagonist.
abstract: Indolic N-benzylation of naltrindole reportedly extends the duration of delta-opioid receptor (DOR) antagonism. Similar modification of the kappa-opioid receptor (KOR) antagonist norBNI (1a) and its 17,17'-diNMe analogue (1d), a low potency mu-opioid receptor (MOR) partial agonist, was found to affect predominantly their MOR activity. When administered systemically in mouse antinociceptive assays, N-benzyl-norBNI (1b) had only MOR agonist activity of relatively short duration whereas on central administration it had only a KOR-antagonist action of extremely long duration.
authors.affiliation: Department of Pharmacy and Pharmacology, University of Bath, Bath BA2 7AY, UK.
authors.forename: Cédric
authors.initials: C
authors.lastname: Chauvignac
authors.forename: Carl N
authors.initials: CN
authors.lastname: Miller
authors.forename: Sanjay K
authors.initials: SK
authors.lastname: Srivastava
authors.forename: John W
authors.initials: JW
authors.lastname: Lewis
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Husbands
authors.forename: John R
authors.initials: JR
authors.lastname: Traynor
mesh_terms: D000700:Analgesics / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006801:Humans; D051379:Mice; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011758:Pyrroles / Q000737:chemistry*; D011869:Radioligand Assay; D017465:Receptors, Opioid, delta / Q000187:drug effects; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors*; D017450:Receptors, Opioid, mu / Q000819:agonists; D013329:Structure-Activity Relationship
chemical_list: C499148:17,17'-bis(cyclopropylmethyl)-6,6',7,7'-tetrahydro-4,5-4',5'-diepoxy-6,6'-(benzylimino)(7,7'-bimorphinan)-3,3',14,14'-tetrol; D000700:Analgesics; D011758:Pyrroles; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; C051844:norbinaltorphimine; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D009271:Naltrexone