A Correlation of Kappa Receptor Binding with Spinal Kappa Analgesia
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Authors
Gorman, Stephanie C.
Issue Date
1996
Type
Thesis
Language
en_US
Keywords
Alternative Title
Abstract
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.
Description
vi, 23 p.
Citation
Publisher
Kalamazoo College
License
U.S. copyright laws protect this material. Commercial use or distribution of this material is not permitted without prior written permission of the copyright holder.