Alkylation of opioid receptor subtypes by .alpha.-chlornaltrexamine produces concurrent irreversible agonistic and irreversible antagonistic activities
.alpha.-Chlornaltrexamine (1a, .alpha.-CNA), the C-6 epimer of the opioid receptor affinity label .beta.-CNA (1b), was synthesized and tested in vitro and in vivo. In vitro, .alpha.-CNA appears to alkylate opioid receptor subtypes (.mu., .kappa. and .delta.) and is similar to .beta.-CNA in its ability to produce irreversible antagonism at all 3 subtypes. However, 1a differs from 1b in that it exhibits additionally an irreversible agonist activity in the guinea-pig ileum preparation but not in the mouse vas deferens preparation. This latter activity is discussed in terms of an irreversible mixed agonism-antagonism at .kappa. receptors, or, alternatively, it may reflect differences between .mu. receptors in the 2 in vitro preparations.