Specific opiate receptors were identified in the period 1971-1973. These receptors combine in a stereospecific manner with all the known active opiates and opiate antagonists. This combination can be demonstrated physically with radioactive opiate ligands. Opiate receptors are found only in the nervous systems of vertebrates. Naloxone is a specific opiate antagonist, which blocks and reverses the effects of morphine, meperidine, methadone, fentanyl and other opiate agonists. Thus, naloxone is highly effective in the treatment of opiate overdosage, and it is the agent of choice for such treatment. The specificity of these receptors suggested that their real function was to combine with an endogenous ligand. A deliberate search for endogenous ligands resulted, in 1975, in the discovery of endorphins, peptides with opiate-like pharmacologic action. Two pentapeptides in brain, called enkephalins, have the structure tyrosine-glycine-glycine-phenylalanine-methionine (methionine-enkephalin) and tyrosine-glycine-glycine-phenylalanine-leucine (leucine-enkephalin). These pentapeptides are present throughout the brain and spinal cord at various densities in different regions. A prominent association is between enkephalins and the pain pathways. Just as naloxone blocks the opiate receptors when true opiates are the agonists, so does it block the opiate-like actions of enkephalin. General anesthetic agents may release enkephalin (or other endorphins) at opiate receptor sites in the pain pathways, and it is possible that the analgesic component of general anesthesia is due to this enkephalin release.