Pharmacology
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Midazolam, a benzodiazepine receptor agonist, when injected intrathecally either enhances or decreases antinociception produced by intrathecal administration of morphine in rats. Furthermore, midazolam inhibits binding of several opioid ligands to spinal opioid receptors in vitro [Rattan et al, Anesth Analg 1991;73:124-131]. This study was designed to investigate the effect of midazolam on binding of mu-, delta- and kappa-ligands to rat spinal opioid receptors in the presence of sodium ions which differentially modulate binding of opioid agonists and antagonists. ⋯ Scatchard analysis performed in the presence of sodium ions and/or midazolam confirmed the specific effects of sodium ions as well as midazolam on the Bmax and KD of mu-, delta-, and kappa-receptors. These results suggest for the first time that sodium ions play an important role in the modulation of spinal opioid receptors by benzodiazepines. Sodium ions potentiate the inhibition of DAGO binding but antagonize the inhibition of naloxone and DSTLE binding by midazolam in rat spinal cord.