Wake-up call for a new drug

Falling asleep without warning may be due to narcolepsy, an embarrassin g and even dangerous syndrome. Jeremy Laurance on a drug that may also help others who need to stay awake

A drug that prevented sleep without causing ill effects would be a pharmaceutical miracle. It would earn billions for the company discovering it, and it could change modern life.

It would have to be more effective than cups of black coffee, but without the side-effects of amphetamine-based stimulants. All-night party-goers could pop a pill with the breakfast orange juice and arrive at work unfazed. Students revising into the small hours could turn up for exams with their minds pin-sharp. Armies could fight through the day and march through the night.

We do not yet have such a drug, but the most promising candidate is now being examined in Britain. Called Modafinal, it has already been investigated by military organisations in France, the US and Britain, where keeping weary soldiers alert can prolong their lives.

Initially, the drug is being tested as a treatment for narcolepsy, a rare disorder marked by an intense and overwhelming need to sleep that can strike at any time. The attacks, which usually last from 10 to 15 minutes, can even occur when sufferers are walking in the street.

David Parkes, professor of clinical neurology at the Institute of Psychiatry, London, and the UK's leading expert on narcolepsy, says that Modafinal is a novel compound with unusual characteristics.

"It is a fascinating drug. It has a completely different mode of action on the brain from anything else. Amphetamine-based drugs work by stimulating noradrenaline, the 'fight or flight' hormone. They can cause aggression in high doses - people push beer mugs into each other's faces. But Modafinal has no effect on noradrenaline, and it is conceivable that it has no effect on aggression."

However, it is not yet clear whether it would be more effective than existing treatments for narcolepsy, Professor Parkes says. "Its manufacturers are claiming that it is sleep-preventing rather than a stimulant. It may have some potential in promoting wakefulness if that is not followed by rebound sleepiness when the drug wears off. With every drug currently available, there is a downside. There is some evidence that with Modafinal, there may be no rebound sleep effect."

If proved safe and effective, Modafinal might be used as a treatment for jet lag, or for disrupted sleep caused by shift work. It could also, paradoxically, have potential as a treatment for insomnia - by preventing sleepiness during the day and thus promoting sleep at night.

Experts, however, remain sceptical that any stimulant drug can have no downside, and warn that even if it is not chemically addictive, it may be open to abuse. They say it may not give the buzz that other drugs do, but reports from the US suggest that it does have a euphoriant effect.

Dr Meryl Dahlitz, a researcher on narcolepsy at King's College Hospital who is working with Professor Parkes, says promoters of the drug have argued that it has no potential for abuse because it is not a stimulant. "That seems to be stretching a point," she says. "Uppers and downers are often abused, and since Modafinal is not on the market yet, we cannot know whether it will be abused."

Professor Jim Horne, director of the sleep research laboratory at Loughborough University, says that military interest in the drug has been considerable. "It has been used by the US Army to keep soldiers awake for long periods during military operations. But there are some problems with it. The jury is still out."

The drug is available only on a compassionate, named-patient basis to narcoleptics in Britain - and only if their GPs are prepared to pay the cost - around pounds 3,000 a year.

In the US, it is being heavily promoted as a new approach to the treatment of narcolepsy, which affects 150,000 people who need drug treatment throughout their lives. Although the cost is many times higher than existing amphetamine- based drugs, there will be only one or two patients on each family doctor's list, and the drug companies are hoping it will not make too big a hole in their budgets.

For many victims of narcolepsy, existing treatments leave their symptoms inadequately controlled. Sedatives that improve sleep at night have a hangover effect which leaves sufferers sleepier next day. Stimulants, on the other hand, keep sufferers alert during the day but give them insomnia the next night. "They end up chasing their tails," Dr Dahlitz says.

It has, nonetheless, proved difficult to persuade GPs to foot the bill. "Most say no, because it is expensive and the alternatives such as amphetamines are cheap. It is hard to justify the extra cost," she points out.

The French manufacturers of Modafinal, Laboratoire Lafonte, expect to apply for a product licence in the UK later this yearn