Corrections to Design, Synthesis, and Biological Evaluation of 6α- and 6β-N-Heterocyclic Substituted Naltrexamine Derivatives as μ Opioid Receptor Selective Antagonists

Abstract

Page 1418. Lines 3-6 in the right column should be as follows:Molecular Design. On the basis of the molecular modeling study, two series of ligands were designed as MOR selective antagonists (Table 1). While some of these ligands have been reported previously for various purposes (e.g. control compound 8, 1 compounds 2 and 8, 2,3 and control compounds 15 and 16, 4 ), to our knowledge none of them have been discussed specifically in the literature as selective μ opioid receptor antagonists.References for the above paragraph are as follows: J. R. Synthesis and biological evaluation of alpha-and beta-6-amido derivatives of 17-cyclopropylmethyl-3,14beta-dihydroxy-4,5alpha-epoxymorphinan: potential alcohol-cessation agents.

Methylation Products of 6β-N-Heterocyclic Substituted Naltrexamine Derivatives as Potential Peripheral Opioid Receptor Modulators

“…To determine whether these compounds may be centrally acting, a tail immersion assay was conducted to find out whether dMNAP and dMNMP produced antinociception or blocked morphine's antinociceptive effects by subcutaneous injection (s.c.). 39,42 As observed in Figure 2A, dMNAP at a dose of 10 mg/kg produced insignificant antinociception compared to morphine (10 mg/kg). dMNMP, on the other hand, did not produce antinociception and its %MPE (the percentage maximum possible effect) was not significantly The values are the mean ± SEM of at least three independent experiments.…”

N -naphthoyl-β-naltrexamine (NNTA), a highly selective and potent activator of μ/κ-opioid heteromers

“…Previous studies using morphine in the same protocol showed a sixfold development of tolerance to i.c.v. morphine (30).…”

“…1) that selectively activates heteromeric μ/κ-opioid receptors in HEK-293 cells. Moreover, NNTA exhibits potent antinociception and lack of physical dependence or conditioned place preference in mice (28)(29)(30).…”

17-Cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-(4′-pyridylcarboxamido)morphinan (NAP) Modulating the Mu Opioid Receptor in a Biased Fashion

“…13−16 Briefly, NAP behaved as a low efficacy MOR partial agonist in the [ 35 S]GTPγS binding assay whereas it also competitively inhibited MOR full agonist [D-Ala 2 -MePhe 4 -Gly(ol) 5 ]enkephalin (DAMGO)-stimulated [ 35 S]GTPγS binding. 13,15 Interestingly, NAP produced no apparent analgesic effects at doses up to 100 mg/kg, while it could antagonize the antinociceptive effect of morphine in the warm water tailimmersion assay with moderate potency. 13 Furthermore, being a P-glycoprotein substrate, NAP has limited access to the central nervous system and dose-dependently restored morphine-impaired intestinal motility without precipitating significant withdrawal symptoms (jumps, wet-dog shakes, or locomotion).…”

“…13,15 Interestingly, NAP produced no apparent analgesic effects at doses up to 100 mg/kg, while it could antagonize the antinociceptive effect of morphine in the warm water tailimmersion assay with moderate potency. 13 Furthermore, being a P-glycoprotein substrate, NAP has limited access to the central nervous system and dose-dependently restored morphine-impaired intestinal motility without precipitating significant withdrawal symptoms (jumps, wet-dog shakes, or locomotion). 14,16 While originally NAP was defined as a potent antagonist on the MOR due to its lack of efficacy from our in vivo studies, its partial agonism on the MOR from the in vitro experiment results really intrigued us.…”