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

• Published in: Brain research 2003-02, Vol.964 (2), p.302-305
• Main Authors: Lewanowitsch, Tanya, Irvine, Rodney James
• Format: Article
• Language: English
• Subjects: Analgesics, Opioid - pharmacology; Animals; Benzeneacetamides; Biological and medical sciences; Brain - drug effects; Brain - metabolism; Enkephalin, Ala-MePhe-Gly- - pharmacology; Enkephalin, D-Penicillamine (2,5)- - pharmacology; Male; Medical sciences; Mice; Mouse; Naloxone; Naloxone - analogs & derivatives; Naloxone - metabolism; Naloxone - pharmacology; Naloxone methiodide; Narcotic Antagonists - metabolism; Narcotic Antagonists - pharmacology; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Opioid receptor; Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems; Pharmacology. Drug treatments; Pyrrolidines - pharmacology; Quaternary Ammonium Compounds; Receptors, Opioid, delta - agonists; Receptors, Opioid, delta - metabolism; Receptors, Opioid, kappa - agonists; Receptors, Opioid, kappa - metabolism; Receptors, Opioid, mu - agonists; Receptors, Opioid, mu - metabolism; Tritium
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/S0006-8993(02)04117-3

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 [ 3H]DAMGO, [ 3H]DPDPE and [ 3H]U-69,593 to compare the ability of naloxone and naloxone methiodide to displace binding to μ, δ and κ 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 μ, 6:1 for κ and 330:1 for δ 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.