3-Methoxynaltrexone, a selective heroin/morphine-6β-glucuronide antagonist Journal Article
| Authors: | Brown, G. P.; Yang, K.; King, M. A.; Rossi, G. C.; Leventhal, L.; Chang, A.; Pasternak, G. W. |
| Article Title: | 3-Methoxynaltrexone, a selective heroin/morphine-6β-glucuronide antagonist |
| Abstract: | Recent work has suggested that heroin and morphine-6β-glucuronide (M6G) both act through a novel mu opioid receptor subtype distinct from those mediating morphine's actions. This very high affinity 3H-M6G site is selectively competed by 3-methoxynaltrexone. In vivo, 3-methoxynaltrexone (2.5 ng, i.c.v.) selectively antagonizes the analgesic actions of heroin and M6G without interfering with mu (morphine and [D-Ala2,MePhe4,Gly(ol)5]enkephalin), delta ([D-Pen2,D-Pen5] enkephalin), kappa1 (U50,488H) or kappa3 (naloxone benzoylhydrazone) analgesia. In dose-response studies, 3-methoxynaltrexone (2.5 ng, i.c.v.) significantly shifted the ED50 values for heroin and its active metabolite, 6-acetylmorphine, without affecting the morphine curve. These results indicate that 3-methoxynaltrexone selectively blocks a novel 3H-M6G binding site which is responsible for the analgesic actions of heroin and M6G. This ability to selectively antagonize heroin actions opens new possibilities in the development of therapeutics for the treatment of opioid abuse. |
| Keywords: | controlled study; unclassified drug; dose response; nonhuman; mouse; animals; mice; animal tissue; animal experiment; transfection; drug selectivity; animalia; drug antagonism; binding sites; receptor affinity; morphine; opioid; drug metabolite; drug binding site; analgesia; mu opiate receptor; receptors, opioid, mu; receptor binding; binding competition; diamorphine; enkephalin[2,5 dextro penicillamine]; morphine 6 acetate; morphine 6 glucuronide; naltrexone; heroin; opiate addiction; tritium; opioid receptor; cho cells; cricetinae; delta opiate receptor; receptor subtype; binding, competitive; opiate antagonist; 3,4 dichloro n methyl n [2 (1 pyrrolidinyl)cyclohexyl]benzeneacetamide methanesulfonate; naloxone benzoylhydrazone; kappa opiate receptor; radioligand; enkephalin[2 dextro alanine 4 methylphenylalanine 5 glycine]; narcotic antagonists; mu receptor; subcutaneous drug administration; opiate agonist; morphine derivatives; intracerebroventricular drug administration; brain homogenate; male; priority journal; article; 3 methoxynaltrexone; n methyllevallorphan |
| Journal Title: | FEBS Letters |
| Volume: | 412 |
| Issue: | 1 |
| ISSN: | 0014-5793 |
| Publisher: | Wiley Blackwell |
| Date Published: | 1997-07-21 |
| Start Page: | 35 |
| End Page: | 38 |
| Language: | English |
| DOI: | 10.1016/s0014-5793(97)00710-2 |
| PUBMED: | 9257684 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 17 March 2017 -- Source: Scopus |
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