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Type: Journal article
Title: Relationship between 4,5-epoxymorphinan structure and in vitro modulation of cell proliferation
Author: Hutchinson, M.
Somogyi, A.
Citation: Behavioural Processes, 2004; 494(2-3):251-262
Publisher: Elsevier Science BV
Issue Date: 2004
ISSN: 0014-2999
Statement of
Mark R. Hutchinson and Andrew A. Somogyi
Abstract: Abstract Morphine belongs to the class of compounds known as 4,5-epoxymorphinans, which can alter immune function directly via receptors expressed by immune cells. However, the opioid characteristics of these receptors are not clear. Therefore, the aim of this study was to investigate the in vitro immunomodulatory effects of 24 structurally related 4,5-epoxymorphinans to allow further characterisation of the receptor that mediates the immunomodulation and to ascertain if there is any structure-effect relationship. The immunomodulation of 4,5-epoxymorphinans using isolated mouse splenocytes stimulated with concanavalin A resulted in five types of responses: an inverted bell shaped curve (oxycodone, inhibitory EC50=1.6 nM), an inhibitory concentration response curve (buprenorphine, inhibitory EC50=12.6 μM), an inverted bell-shaped curve with induction (morphine, induction EC50=1.7 μM), an induction concentration response curve (oxymorphone, induction EC50=20 nM), and the lack of any response (e.g. noroxycodone). Non-stereoselectivity, naloxone-insensitivity, naloxone-sensitivity and non-classical opioid rank order of effect were all observed. A structure-effect relationship was developed and significant evidence for non-classical opioid receptor function on immune cells was concluded.
Keywords: Opioid
immune system
cell proliferation
structure–effect relationship
Description: Copyright © 2004 Elsevier B.V. All rights reserved.
DOI: 10.1016/j.ejphar.2004.04.049
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Pharmacology publications

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