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Modafinil: The Ultimate Wake-up Pill?

Modafinil: The Ultimate Wake-up Pill? (<i>cont'd</i>)

The military has a high-stake interest in this new drug. Wartime missions often require sleep deprivation of pilots. Vietnam War aircrews were the first to widely use amphetamines. More recently, the Air Force gave Dexedrine to most flight crews during the Persian Gulf War. More than 60 percent of those who used it said it had been "essential" to accomplishing their mission.

Beyond the military, there is huge mainstream potential for a drug that would keep people awake and alert without significant side effects. Shift workers and those looking to take on another job or expand their hours of productivity could benefit.

"It can keep you more alert, but whether it can keep you at full mental performance remains to be seen," says Scammell. "Can a surgeon still operate with the same precision?"

Although modafinil has inspired much research, relatively little is actually known about how it works. "The fundamental mechanism remains obscure," says Scammell.

Brain cells, also known as neurons, rely on neurotransmitters like dopamine, to communicate with each other. One neuron releases a neurotransmitter, which relays a message to the next one. The brain's neurons serve many distinct functions. Some are involved in making you fall asleep, while others wake you up. One thing that scientists have learned in recent years is that the systems that put you to sleep probably do so by shutting off the ones that promote wakefulness and vice versa.

Dopamine plays an important role in one of the wake-promoting pathways in the brain. One of the primary ways amphetamines keep people awake is by blocking protein structures known as transporters from reabsorbing the neurotransmitters back into the cells that released them.

One of the ways in which modafinil works could be similar, affecting the neurotransmitter dopamine, Scammell says. One study, conducted by him and his colleagues, found the drug activated rat brain neurons that normally respond to dopamine. A different study by Stanford researchers reported that rats that lacked a reuptake transporter for dopamine did not respond to modafinil.

Because modafinil seems like such a great fix to a sleepy problem, Scammell says he worries that people with real medical reasons for their sleepiness, such as sleep apnea, will take the medication instead of getting a proper evaluation by their doctors. And ultimately, there's nothing like the real thing. "As best as I'm aware, if you're really sleep-deprived, it doesn't matter how many stimulants you give somebody," he says. "There's no substitute for sleep."

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