naloxazone and naloxonazine

In addition to morphine-selective mu 2 and enkephalin-preferring delta sites, recent evidence supports the presence within the central nervous system of a common site with very high affinity for both enkephalins and opiates termed the mu 1 site. This concept of a common, very high affinity site for multiple neurotransmitters is a unique concept in neuropharmacology, differing from classical transmitter systems which possess multiple receptor classes for a single transmitter. This review will address both the biochemical and pharmacological evidence supporting the existence of this site.

Topics: Aging; Analgesia; Animals; Autoradiography; Binding, Competitive; Brain; Dihydromorphine; Endorphins; Enkephalin, Leucine; Enkephalin, Leucine-2-Alanine; Enkephalins; Ethylmaleimide; Morphine; Naloxone; Neurotransmitter Agents; Phylogeny; Receptors, Opioid; Receptors, Opioid, mu; Respiration; Substance-Related Disorders; Tissue Distribution

Further investigations into the molecular actions of the 14-hydroxydihydromorphinone hydrazones (naloxazone, oxymorphazone, and naltrexazone) have suggested that their irreversible actions can be explained by the formation of their azines. These azines, naloxonazine, naltrexonazine, and oxymorphonazine, irreversibly block opiate binding in vitro 20- to 40-fold more potently than their corresponding hydrozones, naloxazone, naltrexazone, and oxymorphazone. The blockade of binding by naloxonazine shows the same selectivity for high affinity, or mu1, sites as naloxazone.

Topics: Animals; Brain; Cell Membrane; Dihydromorphine; Drug Stability; Hydromorphone; Kinetics; Naloxone; Naltrexone; Oxymorphone; Receptors, Opioid; Structure-Activity Relationship