A potential probe for examining opiate-receptor interactions: model compound study of dynamic effects on 15N INEPT...

Model systems were chosen in an attempt to mimic the proton exchange environment of an agonist nitrogen in an opiate-receptor interaction. The two model systems studied were an ammonium: 18-crown-6 ether complex and a quinuclidine-trifluoroacetic acid ion pair. Each system was examined for their effects on 15N NMR INEPT enhancements. Both models were found to retard proton exchange dynamics, as observed by increased enhancements relative to free ions in neutral aqueous solutions. These results suggest that the confinement of a protonated nitrogen, such as that expected in receptor binding, may alter exchange dynamics to favor INEPT enhancements, while unbound agonists would remain unenhanced. As a result, 15N NMR INEPT enhancements from a solution of receptor subtypes with an appropriate 15N-labeled agonist may present a means of exploring the dynamics of direct opiate-receptor interactions.