Pharmacological effects of naltriben as a ligand for opioid μ and κ receptors in rat cerebral cortex

Naltriben (NTB) has been used to differentiate the subtypes of δ opioid receptors, δ₁ and δ₂. However, there is considerable evidence suggesting that NTB may act on other types of opioid receptors too. We examined the effects of NTB on the specific binding of radiolabeled ligands for opioid μ and κ₂ receptors, and the effects on the release of [³H]norepinephrine ([³H]NE) in rat cerebral cortex slices. NTB displaced the specific binding of [³H]DAMGO with Ki value of 19.79 ± 1.12 nM in rat cortex membranes. Specific binding of [³H]diprenorphine ([³H]DIP) was inhibited by NTB with Ki value of 82.75 ± 6.32 nM in the presence of DAMGO and DPDPE. High K⁺ (15 mM)-stimulated release of [³H]NE was attenuated by DAMGO in rat cerebral cortex slices. NTB (30 nM) shifted the dose-response curve of DAMGO to the right and attenuated the maximal effect. In the meantime, NTB inhibited high K⁺-stimulated [³H]NE release at concentrations above 100 nM. The inhibitory effect of NTB was not attenuated by CTAP (10 nM) and naloxone (3 nM) but by higher concentration of naloxone (30 nM), nor-BNI (300 nM) and bremazocine (3 nM). These results indicate that NTB, depending on the dosage, could acts not only as an antagonist at δ but also as a noncompetitive antagonist for μ receptors, and as an agonist for κ₂ receptors in rat cerebral cortex.