14-Methoxymetopon, a very potent μ-opioid receptor-selective analgesic with an unusual pharmacological profile Journal Article
| Authors: | King, M. A.; Su, W.; Nielan, C. L.; Chang, A. H.; Schütz, J.; Schmidhammer, H.; Pasternak, G. W. |
| Article Title: | 14-Methoxymetopon, a very potent μ-opioid receptor-selective analgesic with an unusual pharmacological profile |
| Abstract: | 14-Methoxymetopon is a potent opioid analgesic. When given systemically, it is approximately 500-fold more active than morphine. However, this enhanced potency is markedly increased with either spinal or supraspinal administration, where its analgesic activity is more than a million-fold greater than morphine. It was μ-opioid receptor selective in binding assays and its analgesia was blocked only by μ-opioid receptor-selective antagonists. Yet, it had a different selectivity profile than either morphine or morphine-6β-glucuronide. Unlike morphine, 14-methoxymetopon was antagonized by 3-O-methylnaltrexone, it was sensitive to antisense probes targeting exons 1, 2 and 8 of the opioid receptor gene and was inactive both spinally and supraspinally in CXBK mice. Although it retarded gastrointestinal transit, it displayed a ceiling effect with no dose lowering transit by more than 65%, in contrast to the complete inhibition of transit by morphine. These finding demonstrate that 14-methoxymetopon is a highly potent μ-opioid with a pharmacological profile distinct from that of the traditional μ-opioid morphine. © 2002 Elsevier Science B.V. All rights reserved. |
| Keywords: | controlled study; unclassified drug; exon; nonhuman; binding affinity; mouse; animals; mice; animal experiment; drug potency; dose-response relationship, drug; mice, inbred icr; morphine; pain measurement; analgesics; opioid; gastrointestinal tract; analgesia; mu opiate receptor antagonist; receptors, opioid, mu; analgesic agent; opiate receptor; morphine 6 glucuronide; analgesic activity; injections, intraventricular; 14 methoxymetopon; morphine derivatives; naltrexone derivative; male; priority journal; article; metopon |
| Journal Title: | European Journal of Pharmacology |
| Volume: | 459 |
| Issue: | 2-3 |
| ISSN: | 0014-2999 |
| Publisher: | Elsevier B.V. |
| Date Published: | 2003-01-17 |
| Start Page: | 203 |
| End Page: | 209 |
| Language: | English |
| DOI: | 10.1016/s0014-2999(02)02821-2 |
| PUBMED: | 12524147 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 12 September 2014 -- Source: Scopus |
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