Xenon incorporated in a lipid emulsion inhibits NMDA receptor channels

Abstract

The data demonstrate that Xe dissolved in Lipofundin MCT(R) 20% inhibits NMDA-receptors. Lipid emulsions enriched with Xe may serve as a carrier and a reservoir for Xe.

Evidence That Xenon Does Not Produce Open Channel Blockade of the NMDA Receptor

“…Xe-containing solutions were prepared as previously described (Dinse et al 2005). We did not analyze concentration-response relationships for Xe as even with the maximal concentration of Xe as used here the glutamate activated currents were only blocked by ϳ40% (Weigt et al 2003). The receptor agonists were applied to the cells using the L/M-SPS-8 superfusion system (List, Darmstadt, Germany).…”

The neuroprotective effect and possible therapeutic application of xenon in neurological diseases

“…This is the main mechanism underlying the protective effect of xenon against neuronal damage caused by hypoxicischemic encephalopathy (Banks et al, 2010), traumatic brain injury (Campos-Pires et al, 2019;Coburn et al, 2008;Harris et al, 2013), and epilepsy (Uchida et al, 2012;. Furthermore, in a search for a target for anesthesia induction, xenon was identified as an NMDA receptor antagonist (Franks et al, 1998;Weigt et al, 2003). In neonatal hypoxia-ischemic animal models, the interruption of blood supply to the newborn brain can result in oxygen and glucose transport blockage, leading to a reduction in ATP-dependent capacity substances, Na + /K + pump failure, extracellular ion concentration imbalance, the destruction of synapse function due to continuous membrane depolarization, and the excessive accumulation of extracellular glutamate, thus activating glutamate receptors such as NMDA and α-amino-3-hydroxy-5-methyl-4isoxazolopropionic acid (AMPA) receptors.…”

Intranasal Application of Xenon Reduces Opioid Requirement and Postoperative Pain in Patients Undergoing Major Abdominal Surgery

“…Nasally administered drugs are able to reach the CNS by neural pathways (olfactory and trigeminal) or the bloodstream. 20,21 However, the apolar and highly lipophilic nature of the chemically inert and structureless xenon is well known 10,40 and lipid-soluble agents are absorbed predominantly across the nasal membrane into the bloodstream with a bioavailability of up to 100%. Once in the bloodstream, they can diffuse freely through the blood-brain barrier and reach the CNS.…”

“…This is in accordance with clinical studies using the NMDA receptor antagonists ketamine or dextromethorphan. 4,40 Because fast removal of xenon by exhalation 47,48 after terminating the delivery at the end of surgery is suggested by the kinetic study (see fig. 3), the postoperative effect of xenon is far beyond the duration of its presence in the biophase in concentrations that can provide direct pharmacologic effects.…”