Ketobemidone, an opioid analgesic with NMDA antagonist properties, does not improve metabolism or reduce infarct size after middle cerebral artery occlusion in rats

Recently it was reported that the opioid analgesic ketobemidone in addition to being a potent opioid receptor agonist at the μ receptor also is a weak non-competitive antagonist at glutamate receptors of the NMDA subtype. Since NMDA antagonists consistently reduce infarct volume and improve metabolism in the ischemic penumbra in animal models of ischemic stroke we tested whether ketobemidone would have a similar effect in a rat model of focal cerebral ischemia. By means of quantitative autoradiography, we measured the effect of a 5 mg/kg i.v. bolus injection of ketobemidone on the acute alterations in protein synthesis and glucose consumption in the third hour after proximal, permanent occlusion of the middle cerebral artery occlusion (MCAO). Ketobemidone did not significantly reduce the volume of cortex with reduced protein synthesis or disturbed glucose metabolism. The second part of the study investigated the effect of ketobemidone on the infarct volume 1 day after MCAO. Ketobemidone did not significantly reduce infarct size. Ketobemidone is probably too weak an NMDA antagonist to be neuroprotective in this model of focal cerebral ischemia.