Assessment of the in Vivo and in Vitro Opioid Activity of Bridged Hexahydroaporphine and Isoquinoline Molecules

Victoria F. Roche, Edward B. Roche, Paul K. Lemcke, William S. Wire, Thomas F. Burks

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Four novel racemic bridged hexahydroaporphine (1 and 2) and isoquinoline (3 and 4) analogues have been synthesized in an attempt to generate bicyclic derivatives of the morphinan ring system. The opioid activity of these analogues has been assessed through membrane-binding studies, in vitro studies in isolated guinea pig ileum and mouse vas deferens, and in vivo studies utilizing the mouse hot plate technique. The bridged isoquinoline precursor molecules were inactive as antinociceptives. Both the racemic phenolic hexahydroaporphine 1 and its 10-methoxy congener 2 demonstrated dose-dependent, albeit weak, antinociceptive activity when administered icv, but they induced lethal convulsions when given subcutaneously. The antinociception elicited by 1 appeared to show very weak opioid character while that caused by 2 was totally nonopioid.

Original languageEnglish (US)
Pages (from-to)245-248
Number of pages4
JournalJournal of Medicinal Chemistry
Volume33
Issue number1
DOIs
StatePublished - Jan 1990

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All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery

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