In vivo studies of opiate receptors

To study opiate receptors noninvasively in vivo using positron emission tomography, techniques for perferentially labeling opiate receptors in vivo can be used. The rate at which receptor‐bound ligand clears from the brain in vivo can be perdicted by measuring the equilibrium dissociation constant (K_D) at 37°C in the presence of 100 mM sodium chloride and 100 μM guanyl‐5′‐imidodiphosphate, the drug distribution coeffcient, and the molecular weight. A suitable ligand for labeling opiate receptors in vivo is dipernorphine, which binds to μ, δ and k receptors with apporximately equal affinity in vitro. However, in vivo diprenorphine may bind predominantly to one opiate receptor subtype, possibly the μ receptor. To predict the affinity for binding to the opiate receptor, a Hansch correlation was determined between the 50% inhibitory concentration for a series of halogen‐substituted fentanyl analogs and electronic, lipophilic, and steric parameters. Radiochemical methods for the synthesis of carbon‐11‐labeled diprenorphine and lofentanil are presented.