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Affinities of some common opioid analgesics towards four binding sites in mouse brain

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Summary

The selectivities of morphine, codeine, l-methadone and d-propoxyphene, towards the binding sites in mouse brain membranes labelled by 3H-dihydromorphine (DHM), 3H-ethylketocyclazocine (EKC) and 3H-D-Ala2-Leu5-enkephalin (DALE), were investigated. Of the four binding sites identified, three correspond to mu-, kappaand delta-opioid binding sites or receptors, respectively. The fourth site has a high capacity and binds EKC with a high affinity, DHM with a very low affinity and does not bind DALE. In displacement studies, the relative affinities of morphine and methadone were quite similar towards the tree sites with highest affnity (mu ≫ kappa ≫ delta). Codeine and d-propoxyphene were mu-selective but did not differentiate between kappa-and delta-sites. At high concentrations I-methadone (Kd=6.7 μM), and d-propoxyphene (Kd=40 μM) bound to the fourth site, while morphine, codeine and naloxone were practically inactive. The binding selectivities of these drugs were quite different from those of metkephamid and U-50, 488 H, substances that are thought to exert their antinociceptive effects through delta-and kappa-receptors, respectively. It was concluded that while d-propoxyphene and codeine may partly act througg other receptors than morphine, this is probably not the case for l-methadone.

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  1. Department of Pharmacology, Uppsala University, Box 573, S-751 23, Uppsala, Sweden

    A. Neil

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Neil, A. Affinities of some common opioid analgesics towards four binding sites in mouse brain. Naunyn-Schmiedeberg's Arch. Pharmacol. 328, 24–29 (1984). https://doi.org/10.1007/BF00496100

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  • DOI: https://doi.org/10.1007/BF00496100

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