No doze. When given the drug CX717, sleep-deprived monkeys outperform alert, nondrugged ones in visual matching tests (left). Unlike caffeine and other stimulants, CX717 only works on brain areas needed for the mental task (right).

Staying Smart Without Sleep

Researchers have found a drug that, in monkeys, offsets mental lapses caused by sleep deprivation without the edginess of other stimulants. The finding heightens prospects for a future pill that could restore performance in military pilots, shift workers, and others who function on minimal or irregular sleep.

The drug belongs to a class of compounds called ampakines, which amplify the signal of glutamate, a neurotransmitter important for learning and memory. Unlike caffeine and other stimulants that haphazardly rev up the brain's arousal system, ampakines only work on nerve cells that are already communicating. When given the drug, rats more quickly remember where they've been, and people track moving targets with greater accuracy. However, few have considered testing the brain boosters in those who don't get enough zzz's.

If not for a timely convergence, Sam Deadwyler, a neuroscientist at Wake Forest University School of Medicine in Winston-Salem, North Carolina, probably wouldn't have either. But several years ago, Deadwyler decided to merge the research tools of a collaborator with the goals of a funder. His lab had done rat experiments with ampakines made by Cortex Pharmaceuticals in Irvine, California. He also had U.S. military funds to research strategies for preventing sleep deprivation in pilots. "Well, we have this drug from Cortex," he remarked at the time. "Let's see how it works in the context of sleep deprivation."

In tests of well-rested monkeys, animals receiving the drug, called CX717, performed visual matching tasks--which cued them to find previously viewed images among a hodgepodge of others--more quickly and more accurately than did control subjects. No surprise there. What astounded the researchers were the results of studies in monkeys kept awake for 30 to 36 hours--conditions approximating several days without sleep in humans. As reported 22 August in PLoS Biology, sleep-deprived monkeys who received CX717 consistently outdid their alert, drug-free counterparts in the cognitive tests. Furthermore, brain scans showed increased cerebral activity in the very areas activated during the mental task, demonstrating the drug's specificity.

CX717 may show similar effects in humans. Results of an unpublished Cortex trial performed after the monkey data became available indicate the drug improved wakefulness, memory, and attention in a small group of young British men kept awake for 27 hours.

Deadwyler and colleagues deserve kudos for their "intriguing strategy" of using the drug to counteract sleep loss, says Gary Lynch of the University of California, Irvine, who invented ampakines. "This could have very, very large social and economic consequences."

Related sites
The paper
Deadwyler's home page