The role of CCK(2) receptors in the homeostasis of the opioid system
by
Noble F, Roques BP.
Department of Structural and Molecular Pharmacochemistry,
Rene Descartes University, Paris, France.
noble@pharmacie.univ-paris5.fr
Drugs Today (Barc). 2003 Nov;39(11):897-908
ABSTRACTPain
The overlapping distribution of opioid and cholecystokinin (CCK) peptides and their receptors (micro- and delta-opioid receptors, CCK(1) and CCK(2) receptors) in the central nervous system have led to a large number of studies aimed at clarifying the functional relationships between these two neuropeptides. The existence of regulatory loops between both systems has been proposed, and the physiological antagonism between CCK, through activation of CCK(2) receptors, and endogenous opioid systems has been demonstrated. This is illustrated by the large potentiation of the main pharmacological effects of exogenous (morphine) or endogenous (enkephalins) opioids. Thus, co-administration of CCK(2) antagonists with morphine or RB-101, a systemically active inhibitor which fully protects enkephalins from their degradation, led to strongly enhanced analgesic responses or antidepressant-like effects of the opioids. All these findings have been recently confirmed using CCK(2) receptor knockout mice, and the role of CCK(2) receptor in the physiological control of the opioid system has been conclusively demonstrated. In this article, we review the experimental pharmacology of the association of CCK(2) antagonists and opioids (exogenous and endogenous), emphasizing the clinical interest of such an association. (c) 2003 Prous Science. All rights reserved.
Tolerance
Proglumide
Cholecystokinin
Cholecystokinin and chronic pain
Cholecystokinin and delta-opioid regulation
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