Receptors delta analgesic

It is now widely accepted that there are at least three opioid receptor sub-types, mu kappa and delta. During the last decade increasing evidence has accumulated to support the hypothesis that a selective kappa opioid agonist will be a powerful analgesic without the clinically limiting side-effects that characterise morphine (e.g., respiratory depression, constipation, addiction)... 

The biochemical and pharmacological properties of the kappa receptor and the differences between the kappa, mu and delta receptors have been reviewed elsewhere. The reader is directed to the opioid review articles by Rees and Hunter (1990) [4], Casy (1989) [3] and Leslie (1987) [10] and also to two shorter reviews which deal specifically with kappa agonists the review by Horwell published in 1988 entitled Kappa Opioid Analgesics [8] and the review by Millan in 1990 on kappa opioid receptors and analgesia [9]. An account of the medicinal chemistry of selective opioid agonists and antagonists was published in 1990 by Zimmerman and Leander [5]. 

Delta and kappa receptors can also contribute to analgesia, particularly at spinal level. Although morphine also acts on kappa and delta sites but it is not clear that up to what level they contribute in its analgesic action. 

Biochemical studies have shown in vitro and in vivo differential inhib-itory/stimulatory modulation of spinal and supraspinal CCK release by mu and delta opioid agonists. Thus, delta opioid agonists enhance the release of CCK, whereas stimulation of mu opioid receptors reduces its release [81,82], Moreover, it has been shown that activation of CCKi receptors potentiates the analgesic responses induced by mu opioid agonists or by endogenous enkephalins, protected from their catabolism by the dual inhibitor RB 101, while activation of CCK2 receptors reduces them [80]. 

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