Benzomorphans specific receptor sites

Antagonist potencies measured in vitro in the guinea pig ileum system or in vivo by extent of withdrawal in addicted animals should closely parallel the affinity of opiates for the receptor site. Both antagonist potencies and stero-specific binding constants have been measured for a number of N-substituted 5,9 dimethyl 2 hydroxy 6,7 benzomorphan analogues (14, 15, 32). Table III gives these values for the compounds studied and shows the extent of correlation between the known affinities and potencies for four analogues. 

The common features of the local anaesthetic receptor site suggest that novel Na channel blocking drugs could be developed to fit this site that might have higher affinity and specificity than presently available compounds. Consistent with this idea, the novel compound Bill 890 CL, a complex ether of benzoyl and modified benzomorphan moieties, is a potent Na channel blocker binding at the local anaesthetic receptor site with a of 50 nM for the inactivated state (Carter et al 2000). It is aimed for neuroprotective therapy in the treatment of stroke and possibly neurodegenerative diseases. 

Belief in the existence of yet another variety of opioid receptor, designated e, is gaining ground.(228,240) This species was originally postulated to account for the unique characteristics of opioid receptors in the rat vas deferens.<229) /VEndorphin is a potent agonist in this tissue, but its effects do not appear to be mediated at /a-, k-, or 5-sites. Specific benzomorphan sites in rat brain membranes have been described that also do not seem to be of the /c-variety/230 and since /3h-endorphin is likewise a potent ligand for these sites,<231) they may well correspond to the putative e-receptors. 

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