Biochemical and pharmacological evidence for opioid receptor multiplicity in the central nervous system

Evidence from a variety of experimental models has suggested the existence of mu₁, mu₂ and delta binding sites for morphine and the enkephalins in the central nervous system. Additional biochemical experiments now support this concept of a common high affinity site for opiates and opioid peptides. Mu sites have now been implicated in a number of pharmacological actions, including supraspinal analgesia, prolactin release, and catalepsy, but not in others (spinal analgesia, respiratory depression, and the guinea pig ileum). The hypothesis of mu₁ sites was supported by the unique opioid meptazinol, which selectively bound to mu₁ sites. As expected from its mu₁ binding selectivity, its analgesic actions in the mouse, localized supraspinally, were antagonized by the selective mu₁ antagonist naloxonazine and it had no respiratory depressant actions. Other binding studies suggested the presence of discrete SKF10, 047-selective (K_D approximately 5 nM) binding sites in rat brain which differed from both kappa sites and the previously reported PCP-binding sigma sites. Additional binding and autoradiograpical studies have also implied the presence of β-endorphin, or epsilon, sites in the CNS.