The finding "opens a completely original way of dealing with this kind of disarrangement," says Diego Golombek, a chronobiologist at the National University of Quilmes in Buenos Aires, and senior investigator of research that indicates that Viagra prevents time-change fatigue in hamsters. "Moreover, since the drug has been extensively tested in humans—in terms of safety, efficacy and other pharmacological parameters—it could be argued that it should be quite straightforward to start a clinical test."
Jet lag affects the communication between light-responsive photoreceptor cells in the retina of the eye and the hypothalamus, a gland at the base of the brain that connects the nervous and endocrine systems, and, among other things, houses the body's circadian clock. Responding to cues of the light-dark cycle, the clock controls when animals sleep, eat and are active. Traveling through time zones requires adapting to a new light-dark cycle, which can take some people several days.
Sildenafil, the active ingredient in Viagra, is known to inhibit the degradation of cyclic guanosine monophosphate (cGMP), a messenger molecule that advances the body clock in response to light. So researchers assumed, Golombek says, that higher levels would increase the sensitivity of the circadian system and, in the process, "accelerate adaptation to a changing light schedule."
Their results, published in the current issue of Proceedings of the National Academy of Sciences USA: Hamsters given sildenafil (in concentrations of 3.5 parts per million in solution) adjusted to a six-hour change in their light-dark cycle (the equivalent of the time-change experienced by passengers traveling between New York City and Paris) in eight days; it took hamsters injected with saline solution 12 days to recover, as measured by what time they began their daily jog on running wheels in their cages. A larger dose of sildenafil sliced the adjustment time in half to six days, but also brought on penile erections, as the drug was approved to do. Researchers found twice the level of cGMP in the hypothalamuses of hamsters given sildenafil compared with in those of the saline-fed animals.
But there is a hitch: sildenafil only helped hamsters adjust to phase advances of the light-dark cycle time changes—those that would be brought on by eastbound flights across time zones. Golombek speculates that this happened because a different signaling pathway in the hypothalamus governs adaptation to phase delays, like those experienced when entering a time zone that's a few hours behind their body clock.
But doctors probably will not be prescribing the pills for jet lag just yet. There is still more work to be done. Golombek plans to conduct additional studies to determine sildenafil's effects on female hamsters (the current study only involved males), as well as in mice, a model in which much more is known about circadian clock function. If no adverse effects are discovered, the research can move on to clinical trials in humans. "Jet lag trials might involve laboratory simulations," he says. But, we also need 'the real thing,' which means testing pharmacological treatments on long-haul air travel, which will certainly take some time."
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