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MDAN-21 : A Bivalent Opioid Ligand Containing mu-Agonist and Delta-Antagonist Pharmacophores and Its Effects in Rhesus Monkeys
Joint Authors
Aceto, Mario D.
Negus, S. Stevens
Harris, Louis S.
Hughes, Larry D.
Akgün, Eyup
Portoghese, Philip S.
Banks, Matthew L.
Source
International Journal of Medicinal Chemistry
Issue
Vol. 2012, Issue 2012 (31 Dec. 2012), pp.1-6, 6 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2012-04-29
Country of Publication
Egypt
No. of Pages
6
Main Subjects
Abstract EN
MDAN-21, 7′-{2-[(7-{2-[({(5α,6α)-4,5-Epoxy-3,14-dihydroxy-17-methylmorphin-6-yl}-aminocarbonyl)metoxy]-acetylamino}-heptylaminocarbonyl)-methoxy]-acetylamino}-naltrindole, a bivalent opioid ligand containing a mu-opioid receptor agonist (derived from oxymorphone) linked to the delta-opioid receptor antagonist (related to naltrindole) by a spacer of 21 atoms, was reported to have potent analgesic properties in mice.
Tolerance, physical dependence, and conditioned place preference were not evident in that species.
The finding that bivalent ligands in this series, with spacers 19 atoms or greater, were devoid of tolerance and dependence led to the proposal that MDAN-21 targets heteromeric mu-delta-opioid receptors.
The present study focused on its effects in nonhuman primates (Macaca mulatta), a species with a physiology and behavioral repertoire not unlike humans.
With regard to opioids, this species usually better predicts clinical outcomes.
MDAN-21 substituted for morphine in morphine-dependent monkeys in the remarkably low dose range 0.006–0.032 mg/kg, subcutaneously.
Although MDAN-21 failed to produce reliable thermal analgesia in the dose range 0.0032–0.032 mg/kg, intramuscularly, it was active in the same dose range and by the same route of administration, in the capsaicin-induced thermal allodynia assay.
The results suggest that MDAN-21 may be useful in the treatment of opioid dependence and allodynia.
The data provide additional evidence that opioid withdrawal is associated with sensitized pain.
American Psychological Association (APA)
Aceto, Mario D.& Harris, Louis S.& Negus, S. Stevens& Banks, Matthew L.& Hughes, Larry D.& Akgün, Eyup…[et al.]. 2012. MDAN-21 : A Bivalent Opioid Ligand Containing mu-Agonist and Delta-Antagonist Pharmacophores and Its Effects in Rhesus Monkeys. International Journal of Medicinal Chemistry،Vol. 2012, no. 2012, pp.1-6.
https://search.emarefa.net/detail/BIM-463817
Modern Language Association (MLA)
Aceto, Mario D.…[et al.]. MDAN-21 : A Bivalent Opioid Ligand Containing mu-Agonist and Delta-Antagonist Pharmacophores and Its Effects in Rhesus Monkeys. International Journal of Medicinal Chemistry No. 2012 (2012), pp.1-6.
https://search.emarefa.net/detail/BIM-463817
American Medical Association (AMA)
Aceto, Mario D.& Harris, Louis S.& Negus, S. Stevens& Banks, Matthew L.& Hughes, Larry D.& Akgün, Eyup…[et al.]. MDAN-21 : A Bivalent Opioid Ligand Containing mu-Agonist and Delta-Antagonist Pharmacophores and Its Effects in Rhesus Monkeys. International Journal of Medicinal Chemistry. 2012. Vol. 2012, no. 2012, pp.1-6.
https://search.emarefa.net/detail/BIM-463817
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-463817