Dextrorphan binds to opioid receptors in guinea-pig brain membranes and is an antagonist at opioid receptors in myenteric plexus.
Dextrorphan (+)-tartrate, purified by repeated crystallization to remove all traces of the enantiomer levorphanol, binds to mu, delta, and kappa sites on guinea-pig brain membranes with lower affinities (by a factor of 400-3200) than levorphanol. In the guinea-pig ileum myenteric plexus longitudinal muscle preparation (GPI), dextrorphan, at 100-200 microM, inhibits the electrically stimulated twitch, but this action is not blocked or reversed by naloxone; both (+)- and (-)-naloxone produce similar non-opioid twitch inhibition at comparable concentrations. At 10-20 microM, dextrorphan blocks and reverses the twitch inhibition due to mu and kappa agonists, but the blockade can be overcome only partially by increasing the agonist concentration. We conclude that dextrorphan is an opioid ligand with low affinity and with antagonist effect on opioid receptors in the GPI.
Goldstein
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Department of Pharmacology, Stanford University, CA 94305.
Naidu
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D000818:Animals; D001921:Brain / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D003917:Dextrorphan / Q000378:metabolism* / Q000494:pharmacology; D004558:Electric Stimulation; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D007700:Kinetics; D007981:Levorphanol / Q000494:pharmacology; D009019:Morphinans / Q000378:metabolism*; D009022:Morphine Derivatives / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D009197:Myenteric Plexus / Q000378:metabolism*; D009270:Naloxone / Q000494:pharmacology; D009928:Organ Specificity; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism*
D009019:Morphinans; D009022:Morphine Derivatives; D011957:Receptors, Opioid; D003917:Dextrorphan; D007981:Levorphanol; D009270:Naloxone; C010616:normorphine