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 language | English |
|---|---|
| Pages (from-to) | 245-248 |
| Number of pages | 4 |
| Journal | Journal of Medicinal Chemistry |
| Volume | 33 |
| Issue number | 1 |
| State | Published - 1990 |
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All Science Journal Classification (ASJC) codes
- Organic Chemistry
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Assessment of the in vivo and in vitro opioid activity of bridged hexahydroaporphine and isoquinoline molecules. / Roche, Victoria F.; Roche, Edward B.; Lemcke, Paul K.; Wire, William S.; Burks, Thomas F.
In: Journal of Medicinal Chemistry, Vol. 33, No. 1, 1990, p. 245-248.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Assessment of the in vivo and in vitro opioid activity of bridged hexahydroaporphine and isoquinoline molecules
AU - Roche, Victoria F.
AU - Roche, Edward B.
AU - Lemcke, Paul K.
AU - Wire, William S.
AU - Burks, Thomas F.
PY - 1990
Y1 - 1990
N2 - 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.
AB - 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.
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M3 - Article
VL - 33
SP - 245
EP - 248
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
SN - 0022-2623
IS - 1
ER -