Analgesia with kappa opioid agonists

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]. 

Buprenorphine is derived from thebaine. It is a partial mu agonist with kappa antagonist activity. Buprenorphine has 25 to 50 times the potency of morphine. It is used to produce a longer-lasting analgesia than morphine. Effects of buprenorphine last longer because it is released more slowly from mu receptors than morphine. It is available as an injectable for intramuscular (IM) or intravenous administration in a 1-ml solution containing 0.3 mg buprenorphine (as buprenorphine HC1) for the relief of moderate to severe pain. It is also available to treat opioid dependence in the formulation of a tablet,51 alone or in combination with naloxone, in 2- or 8-mg... 

Like other opioid agonists, codeine s major sites of action are localized to and mediated by supraspinal and spinal opioid receptors. Codeine has a low affinity for mu and kappa opioid receptors and its major effects are due to its conversion to morphine. Morphine binds mu opioid receptors with higher affinity, producing dose-dependent analgesia, as well as negative effects typical of mu receptor agonists such as respiratory depression, constipation, and nausea. Codeine also provides clinically useful central antitus-sive effects through a central mechanism that is not completely understood [1]. 

Tramadol is a dual-mechanism, central-acting analgesic. It interacts weakly with p opioid receptors and to a lesser extent at kappa and delta receptors. Interactions at these receptors provide weak opioid agonist properties. It also has effects on noradrenergic and serotonergic reuptake proteins and accentuates spinal and supraspinal monamine-based analgesia [5,6,7]. Tramadol s opioid and non-opioid sites of action appear to act additively to provide more effective pain relief. Of the two tramadol enantiomers, the (+) enantiomer acts as a p receptor agonist and as a 5-HT reuptake inhibitor, while the (-) enantiomer is a norepinephrine reuptake inhibitor [2,5]. 

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