Specific Opiate Receptors Research Articles

Failure of the opiate antagonist naloxone to modify hypnotic analgesia.

Hypnotic analgesia in some respects resembles opiate analgesia. We tested the hypothesis that some features of hypnotic analgesia are mediated through neuronal pathways activating specific opiate receptors in brain. The opiate antagonist naloxone had no effect on hypnotic analgesia in three subjects. Thus, the hypothesis was not confirmed.

Identification of novel high affinity opiate receptor binding in rat brain.

SPECIFIC opiate receptor binding sites1–3, occur in the brains of numerous vertebrates. In our initial studies4–6 binding seemed to involve a homogeneous population of receptors, although the biphasic degradation of receptor binding by trypsin and chymotrypsin suggested more than one site5. We have used 3H-naloxone and 3H-dihydromorphine of very high specific activity, and now report evidence for a new high affinity opiate-binding site in addition to the already reported binding site of lower affinity. The high and low affinity binding site may reflect interactions of opiates with two conformations of the opiate receptor which determine agonist and antagonist actions of the drugs.

The opiate receptor.

Binding of radioactive opiates and opiate antagonists to the opiate receptor in the brain and other tissues can be shown. This binding mediates the pharmacologic effects of the drugs. The regional distribution of the opiate receptor in monkey and human brain parallels the motivational-affective pathways of pain perception and comprises several limbic system structures. In subcellular fractionation experiments, the opiate receptor is localized to synaptic membranes. The influence of sodium on receptor binding permits predictions of the extent to which a drug possesses opiate agonist, antagonist, or mixed properties. The simple, sensitive, and specific opiate receptor binding assay facilitates development of pure opiate antagonists for treating narcotic addiction and mixed agonist-antagonist agents with potential as nonaddicting analgesics.

The depressant action of morphine on transmission at a skeletal neuromuscular junction is non-specific.

Abstract The depressant actions of apomorphine, etorphine, dextromoramide, laevomoramide, naloxone, codeine, morphine and nalorphine have been examined on the rat diaphragm preparation. Their descending order of potency (in the order given above) differed greatly from that published for activity at specific opiate receptors. The depressant action of morphine was not antagonized by naloxone. The stereoisomers dextro- and laevomoramide were equipotent in depressing the preparation. On the transmurally stimulated guinea-pig ileum preparation the depressant action of dextromoramide was antagonized by naloxone. Laevomoramide was 10 000 times less potent than its (+)-isomer, and was not antagonized by naloxone. It is concluded that the effects of narcotic analgesics on transmission at a skeletal neuromuscular junction are not mediated via opiate receptors.