Structural determinants of σ receptor affinity

Abstract

The structural determinants of σ receptor affinity have been evaluated by examining a wide range of compounds related to opioids, neuroleptics, and phenylpiperidine dopaminergic structures for affinity at σ receptor-binding sites labeled with (+)-[3H]3-PPP. Among opioid compounds, requirements for σ receptor affinity differ strikingly from the determinants of affinity for conventional opiate receptors. σ sites display reverse stereoselectivity to classical opiate receptors. Multi-ringed opiate-related compounds such as morphine and naloxone have negligible affinity for σ sites, with the highest σ receptor affinity apparent for benzomorphans which lack the C ring of opioids. Highest affinity ..