The Effects of Xenon and Nitrous Oxide Gases on Alcohol Relapse

Vengeliene, Valentina; Bessière, Baptiste; Pype, J L; Spanagel, Rainer

doi:10.1111/acer.12264

Cited by 8 publications

(1 citation statement)

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“…Extensive research has further revealed some of the underlying mechanisms and include competitive antagonism at the NMDA/AMPA receptor [ 14 ], anti-apoptotic properties (inhibition of mitochondrial cytochrome c release) [ 15 ], activation of pro-survival signaling pathways (increased expression of Bcl-2/Bcl-xL, inhibition of Bax) [ 16 ], MAPK regulation (p38, ERK 1/2 ) [ 17 , 18 ] and potassium ion channels activation (K ATP , TREK-1) [ 19 , 20 ]. The preclinical models suggest potential clinical benefit in indications such as traumatic brain injury, ischemic or hemorrhagic stroke, perinatal hypoxic-ischemic brain injury, coronary artery bypass graft surgery, organ protection during transplantation, chronic pain, and addiction [ 13 , 21 – 23 ]. Any clinical benefit, however, would require chronic (or repetitive) administration of inert gases, in contrast to the currently accepted acute, single administration for the induction and maintenance of general anesthesia (e.g.…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetic analysis of the chronic administration of the inert gases Xe and Ar using a physiological based model

et al. 2015

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BackgroundNew gas therapies using inert gases such as xenon and argon are being studied, which would require chronically administered repeating doses. The pharmacokinetics of this type of administration has not been addressed in the literature.MethodsA physiologically based pharmacokinetics (PBPK) model for humans, pigs, mice, and rats has been developed to investigate the unique aspects of the chronic administration of inert gas therapies. The absorption, distribution, metabolism and excretion (ADME) models are as follows: absorption in all compartments is assumed to be perfusion limited, no metabolism of the gases occurs, and excretion is only the reverse process of absorption through the lungs and exhaled.ResultsThe model has shown that there can be a residual dose, equivalent to constant administration, for chronic repeated dosing of xenon in humans. However, this is not necessarily the case for small animals used in pre-clinical studies.ConclusionsThe use of standard pharmacokinetics parameters such as area under the curve would be more appropriate to assess the delivered dose of chronic gas administration than the gas concentration in the delivery system that is typically reported in the scientific literature because species and gas differences can result in very different delivered doses.

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