THE OPIOID KETOBEMIDONE HAS A NMDA BLOCKING EFFECT

There are clinical observations that neurogenic pain can respond well to the opioid ketobemidone, in contrast to pethidine and morphine. Thi s has led us to the hypothesis that the analgesic effect of ketobemido ne in neurogenic pain may be due to both opioid as well as additional non-opioid effects. The present study was therefore made to evaluate t he effects of ketobemidone. The study consists of two parts. (1) Singl e unit recordings were made from dorsal horn neurones in the halothane -anaesthetised rat. Neurones were activated by transcutaneous electric al stimulation of their receptive fields at C-fibre strength and their responses quantified. The wind-up of the neurones, due to N-methyl-D- aspartate (NMDA) receptor activation, leading to marked increases in C -fibre responses and an associated post-discharge was also measured. K etobemidone, applied to the spinal cord, equivalent to an intrathecal injection, dose-dependently and selectively reduced C-fibre evoked res ponses. Ketobemidone was also found to block wind-up more effectively than morphine at equieffective doses, but unlike morphine in a non-nal oxone-reversible manner. (2) In a binding study ketobemidone was shown to inhibit [H-3]MK-801 binding with a K-i value of 26 mu M. Therefore , ketobemidone appears to possess both mu opioid agonist as well as NM DA blocking effects.