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Assay of 35 S-labeled guanosine-5′- O -(3-thio)triphosphate ([ 35 S]GTP γ S) binding to tissue sections, a method for estimating receptor–G protein coupling in situ, indicates that chronic heroin treatment produced pronounced reductions in MOR activity in several brain regions with an upregulation in total opioid receptor number (Sim-Selley et al., 2000)

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[2] The formulation that reached controlled human testing, and the only one for which a controlled human trial is retrievable, was a topical gel