Pharmacological Characterization of Low-to-Moderate Affinity Opioid Receptor Agonists and Brain Imaging with ¹⁸F-Labeled Derivatives in Rats.

ABSTRACT: The 3,4-dichloro-N-(1-(dimethylamino)cyclohexyl)methyl benzamide scaffold was studied as a template for ¹⁸F-positron emission tomography (¹⁸F-PET) radiotracer development emphasizing sensitivity to changes in opioid receptor (OR) occupancy over high affinity. Agonist potency, binding affinity, and relevant pharmacological parameters of 15 candidates were investigated. Two promising compounds 3b and 3e with μ-OR (MOR) selective agonist activity in the moderate range (EC₅₀ = 1-100 nM) were subjected to ¹⁸F-fluorination, autoradiography, and small-animal PET imaging. Radioligands [¹⁸F]3b and [¹⁸F]3e were obtained in activity yields of 21 ± 5 and 23 ± 4% and molar activities of 25-40 and 200-30

SUBMITTER: Ott J 

PROVIDER: S-EPMC7497404 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature