Abstract
The opioid receptor affinities of butorphanol (BT) and its main metabolites, norbutorphanol(NB) and hydroxybutorphanol(HB), were determined by an in vitro receptor binding assay using crude synaptosomal membrane preparations of rat brain. BT showed high affinities to all types of the receptor except the a type (phencyclidine binding site), resulting in displacements of the bindings of μ (dihydromorphine)-, δ (D-Ala2D-Leu5-enkephalin)-and κ (ethylketocyclazocine)-ligands with more potency than morphine and ketocyclazocine, and it preferentially bound to μ and κ-opioid receptors. NB bound to the μ-binding site with affinity higher than that of pentazocine and to the κ-binding site with the lowest affinity. HB exclusively bound to the μ-binding site with lower affinity. The affinities of BT, NB, HB and morphine to the σ-site were smaller than those of pentazocine and ketocyclazocine. In the presence of 100 mM NaCl or by treating with 500 μM 5, 5'-dithiobis (2-nitrobenzoic acid), the binding capacity of the membrane preparation was altered, and BT behaved as a typical antagonist. NB showed an agonistic property, and HB behaved as an antagonist. BT appears to be a μ-opioid receptor antagonist and has a κ-receptor agonist-like character.
