A Correlation of Kappa Receptor Binding with Spinal Kappa Analgesia
Gorman, Stephanie C.
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Opioid drugs, such as morphine, are frequently used to produce analgesia although they have several adverse side effects. These effects can include tolerance, addiction, respiratory depression and dysphoria. The existence of several opioid receptors and opioid receptor subtypes, specifically the kappa opioid receptors, offers the potential for developing opioid drugs with fewer adverse effects and less abuse potential than those currently available. The purpose of this study was to correlate kappa receptor binding in the guinea pig cerebellum with spinal kappa analgesia in the mouse by using the following six kappa agonist drugs: (-)bremazocine, (+)bremazocine, U50,488, BRL52656-A, BRL53001-A and BRL53117-A. [3H]U69,593 binding to kappa opioid .receptors was performed using guinea pig cerebellum tissue homogenates. Spinal kappa analgesia was measured in mice after 1 µ1 intrathecal injections of drug using the radiant heat tail-flick technique. The six kappa agonists were ranked according to their values of IC50 (inhibitory concentration for 50% specific binding) and ED50 (effective dose inducing analgesia in 50% of subjects) determined from competition curves and dose-response curves, respectively. The agonists were then correlated in a rank order potency comparison. The coefficient of determination for the six kappa agonists was calculated to be 0.95 (p<0.0I). This result suggests a strong correlation between kappa receptor binding and spinal kappa analgesia, which supports the theory that these analgesic effects are possibly mediated by kappa receptors.
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