Naloxone and its quaternary derivative, naloxone methiodide, have differing affinities for μ, δ, and κ opioid receptors in mouse brain homogenates

Naloxone and naloxone methiodide both act on opioid receptors but naloxone methiodide has limited access to the brain. Naloxone methiodide has been shown to have a lower affinity for opioid receptors than naloxone in the rat and guinea pig but has not been tested in the mouse. We aimed to investigate this by using [H-3]DAMGO, [H-3]DPDPE and [H-3]U-69,593 to compare the ability of naloxone and naloxone methiodide to displace binding to mu, delta and kappa opioid receptors in mouse brain homogenates. Significant binding was observed for each receptor type and the binding affinity for naloxone versus naloxone methiodide was found to be 15:1 for mu, 6:1 for kappa and 330:1 for delta receptors. Therefore, naloxone methiodide does have a lower affinity for opioid receptors than naloxone in mouse brain tissue, which must be taken into consideration in experimental designs. (C) 2002 Elsevier Science B.V. All rights reserved.