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.
All Science Journal Classification (ASJC) codes
- Biochemistry, Genetics and Molecular Biology(all)
- Pharmacology, Toxicology and Pharmaceutics(all)