Affinity of naloxone and its quaternary analogue for avian central delta and mu opioid receptors.
Quaternary narcotic antagonists that are assumed not to penetrate the blood-brain barrier following systemic administration are commonly used to distinguish between peripheral and central actions of opiates. In mammals, these antagonists have a lower affinity for opioid receptors than their tertiary parent compounds. The relative affinity of quaternary vs. tertiary antagonists either for opioid receptors in non-mammalian species or for specific receptor subtypes has, however, not been determined. Using brain tissues from a passerine songbird (Junco hyemalis), we found the affinity of the quaternary antagonist, naloxone methiodide (Nal MI), for brain opioid receptors to be less than 10% that of Nal HCl. Further, Nal MI affinity for mu and delta receptors is 8.7% and 3.7%, respectively, that of Nal HCl. These results confirm that tertiary narcotic antagonist quaternization substantially reduces the affinity of these derivatives for central opioid receptors. They show that this reduction is receptor-type selective, and they extend previous reports demonstrating functional similarities between mammalian and non-mammalian central opioid receptors.
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Institute of Arctic Biology, University of Alaska Fairbanks, 99775-7000, USA. ffpjd1@aurora.alaska.edu
D000818:Animals; D001667:Binding, Competitive; D001717:Birds / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D005260:Female; D008297:Male; D009270:Naloxone / Q000031:analogs & derivatives* / Q000378:metabolism*; D000644:Quaternary Ammonium Compounds; D017465:Receptors, Opioid, delta / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000378:metabolism*
D000644:Quaternary Ammonium Compounds; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D009270:Naloxone; C041269:N-methylnaloxone