X-Message-Number: 16219
Date: Mon, 7 May 2001 04:12:42 EDT
Subject: Nitrous Oxide 

I found the following URL of interest on the bio-mechanism of Laughing Gas:


The write-up is included in its entirity directly below:

"How You Make Me Laugh 

Although laughing gas was discovered nearly 200 years ago, how it works in 
the brain has been an enduring mystery. But in this month's Nature Medicine, 
researchers report that nitrous oxide acts like the drug PCP--by blocking the 
brain's NMDA receptors, proteins that play a key role in memory, learning, 
and the perception of pain. Because blocking NMDA receptors can cause brain 
damage, the find raises a caution flag for doctors who use high doses of 
laughing gas.

Nitrous oxide is one of the weakest general anesthetics. Even at 
concentrations of 75%, the gas does not completely knock people out. The 
drug's subtle effect has been difficult to study in cultured cells and in 
laboratory animals. Anesthesiologist Vesna Jevtovic-Todorovic and her 
colleagues at Washington University School of Medicine in St. Louis skirted 
that problem by using a high-pressure chamber, which allowed them to 
administer high doses of nitrous oxide to rats and still include oxygen in 
the mix, so the animals did not suffocate. 

The researchers came up with several lines of evidence suggesting that 
nitrous oxide blocks NMDA receptors. The gas prevented brain damage in rats 
that would have been caused by high NMDA doses. In addition, electrical 
measurements from rat brain cells in culture showed that nitrous oxide cuts 
NMDA-type signaling in half, but has only a small effect on GABA-type 
signaling, the other common pathway affected by anesthetics. Finally, high 
doses of the drug damaged the same brain cells as the hallucinogenic drug 
phencyclidine (PCP) and the anesthetic ketamine, both known NMDA-blockers. 

The doses that cause cell death in rats, when extrapolated to humans, are not 
much higher than those commonly used by doctors and dentists, warns 
Jevtovic-Todorovic. Fortunately, because of its low potency, laughing gas is 
usually combined with other anesthetics--often those that affect GABA 
receptors. For unknown reasons, such drugs can protect against the toxic 
effects of NMDA blockers. But giving laughing gas on its own--or, perhaps 
worse, in combination with ketamine--"is something that really has to be 
thought about and looked at more carefully," says biophysicist Nicholas 
Franks of Imperial College in London.


David C. Johnson, Raleigh

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