Interaction of dextrorotatory opioids with phencyclidine recognition sites in rat brain membranes |
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Authors: | TF Murray ME Leid |
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Institution: | College of Pharmacy Oregon State University Corvallis, OR 97331, USA |
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Abstract: | The potencies of several dextrorotatory opioids, including four pairs of enantiomers, as inhibitors of specific 3H]PCP binding to rat brain synaptic membranes has been determined. Of the compounds tested unlabeled phencyclidine (PCP) was the most potent followed by (?)? cyclazocine > dextrorphan > (+) ketamine > (+) cyclazocine > (+)? SKF10,047 > levorphanol > dextromethorphan > (?) SKF10,047 > (?)? ketamine > (±) pentazocine and > (±) ethylketocyclazocine. The opiate mu receptor ligands, morphine, naloxone and naltrexone were virtually inactive as competitors of specific 3H]PCP binding. Unlike the stereostructural requirements for opiate mu receptors where activity resides predominantly in the levorotatory enantiomers, the present results support the contention that binding to the 3H]PCP labeled recognition site may reside in either the levorotatory or the dextrorotatory enantiomer. The specific binding of 3H]PCP which was defined as total binding minus that occurring in the presence of 10μM dextrorphan was found to be of a high affinity, saturable, reversible and sensitive to thermal degradation. These results suggest that certain dextrorotatory morphian derivatives may prove to be useful probes in further investigations of the molecular characteristics of the 3H]PCP binding site in brain membrane preparations. |
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Keywords: | to whom correspondence should be addressed |
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