Nitrous Oxide Neurotoxicity Studies in Man and Rat

Dyck, Peter James; Grina, Lucy A.; Lambert, Edward H.; Calder, C.; Oviatt, Karen F.; Rehder, Kai; Lund, Bruce A.; Skau, Kenneth A.

doi:10.1097/00132586-198112000-00031

Cited by 3 publications

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“…O ver the past 10 yr , major progress has been made regarding the molecular mechanisms by which the remarkably safe inhalational clinical anesthetics xenon (Xe) and nitrous oxide (N 2 O) act to produce their pharmacological neuroprotective and anesthetic action (1–5). In contrast to most inhalational clinical anesthetics, which act by potentiating the type A γ‐aminobutyric acid receptor, Xe and N 2 O possess low‐affinity antagonistic properties at the N ‐methyl‐ d ‐aspartate (NMDA) and neuronal nicotinic receptors (6–8) and further act on other neuronal targets, such as globular proteins (9).…”

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confidence: 99%

Pressure‐response analysis of anesthetic gases xenon and nitrous oxide on urate oxidase: a crystallographic study

et al. 2011

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The remarkably safe anesthetics xenon (Xe) and, to lesser extent, nitrous oxide (N(2)O) possess neuroprotective properties in preclinical studies. To investigate the mechanisms of pharmacological action of these gases, which are still poorly known, we performed both crystallography under a large range of gas pressure and biochemical studies on urate oxidase, a prototype of globular gas-binding proteins whose activity is modulated by inert gases. We show that Xe and N(2)O bind to, compete for, and expand the volume of a hydrophobic cavity located just behind the active site of urate oxidase and further inhibit urate oxidase enzymatic activity. By demonstrating a significant relationship between the binding and biochemical effects of Xe and N(2)O, given alone or in combination, these data from structure to function highlight the mechanisms by which chemically and metabolically inert gases can alter protein function and produce their pharmacological effects. Interestingly, the effects of a Xe:N(2)O equimolar mixture were found to be equivalent to those of Xe alone, thereby suggesting that gas mixtures containing Xe and N(2)O could be an alternative and efficient neuroprotective strategy to Xe alone, whose widespread clinical use is limited due to the cost of production and availability of this gas.

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confidence: 99%

Pressure‐response analysis of anesthetic gases xenon and nitrous oxide on urate oxidase: a crystallographic study

et al. 2011

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“…Nitrous oxide can be a health hazard after prolonged exposure to low concentrations. [3][4][5] Nitrous oxide is teratogenic in rats, whereas xenon is not. 6 Also, xenon is harmless to the ozone layer and probably more potent than nitrous oxide.…”

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Comparison of the analgesic potency of xenon and nitrous oxide in humans evaluated by experimental pain

Petersen-Felix

Luginbühl

Schnider

et al. 1998

British Journal of Anaesthesia

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We have compared the analgesic potency of MAC-equivalent concentrations of xenon (10, 20, 30 and 40%) and nitrous oxide (15, 30, 45 and 60%) in humans using a multimodal experimental pain testing and assessment technique. We tested 12 healthy volunteers in a randomized, single-blind, crossover study. The following experimental pain tests were used: nociceptive reflex to repeated stimuli; pain tolerance to maximal effort tourniquet ischaemia; electrical stimulation; mechanical pressure; and cold. Reaction time was also measured. Xenon and nitrous oxide produced analgesia to ischaemic, electrical and mechanical stimulation, but not to cold pain. There was no difference in MAC-equivalent concentrations of xenon and nitrous oxide. Both increased reaction time in a similar manner. Xenon and nitrous oxide evoked nausea and vomiting in a large number of volunteers.

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“…Clinical studies identified neuropathy subsequent to chronic abuse of this anesthetic gas (Layzer et al, 1978), and animal studies demonstrated changes in nerve tissue following experimental exposures (Dinn et al, 1980; Van der Westhuyzen et al, 1982). The fetus is reported to be even more susceptible to N20 than the adult (Vieira et al, 1980;Dyck et al, 1980), such that hyporeactive startle reflexes can be readily demonstrated subsequent to in utero exposures of mice (Rice and Millan, 1985). These studies generally link N20 with adverse effects upon the peripheral nervous system; however, its overall impact upon the central nervous system and subsequent functional output has yet to be delineated.…”

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Behavioral Toxicity of Nitrous Oxide in Rats Following Prenatal Exposure

Mullenix¹,

Moore

Tassinari³

1986

Toxicol Ind Health

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Nitrous oxide (N2O) exposure has been associated with neurotoxicity, especially peripheral neuropathy, in both humans and animals. The effects of this anesthetic gas on the central nervous system (CNS) and spontaneous behavior, however, have yet to be delineated. Timed-pregnant Sprague-Dawley rats were exposed to 75% N2O/25% O2 on gestational days 14 and 15 or day 15 only for eight hours per day. The offspring were tested at one and five months of age; their spontaneous behavior in a novel environment was recorded in the residential maze and using time-lapse photography. The results indicated that in utero exposure to N2O permanently altered the spontaneous motor output of the CNS. This effect was most prominent in 5 month old animals, and females were affected more than males. Exposures on gestational days 14 and 15 produced an effect that was not only greater but also qualitatively different than that produced by exposure on day 15 only. The two-day exposure induced hyperactivity in both sexes, whereas the one-day exposure induced hyperactivity in the males and slight hypoactivity in the females. These behavioral changes were not accompanied by physical abnormalities but nonetheless were lasting effects in need of further consideration.

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Nitrous Oxide Neurotoxicity Studies in Man and Rat

Cited by 3 publications

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Pressure‐response analysis of anesthetic gases xenon and nitrous oxide on urate oxidase: a crystallographic study

Pressure‐response analysis of anesthetic gases xenon and nitrous oxide on urate oxidase: a crystallographic study

Comparison of the analgesic potency of xenon and nitrous oxide in humans evaluated by experimental pain

Behavioral Toxicity of Nitrous Oxide in Rats Following Prenatal Exposure

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