神奇鼻喷剂,竟能代替睡眠?

【神奇鼻喷剂,竟能代替睡眠?】如果你相信十几年前读过的一篇文章的标题的话,你可能会认为2016年的元旦,在一系列的庆祝活动后我们仍会保持清醒,神奇的鼻喷剂代替了睡眠。
这种药物叫做Orexin-A,2007年介绍它的文章名为“吸入大脑需要的化学物质可以代替睡眠”和“DARPA开发大脑化学物质来代替睡眠”。
那时,这项研究由加州大学洛杉矶分校的Jerry Siegel教授领导,他对ABC News介绍到“新的研究发现这种提神的新方法是良性的。”传言这种新的药物可以成为睡眠替代剂并且不会产生例如上瘾以及情绪波动等负面影响,不像它的前任咖啡因药片、兴奋剂以及安非他命会产生一些列的副作用却没有任何效果。
在这项研究中,一群实验室的猴子在被剥夺睡眠30到36个小时后使用鼻喷剂或安慰剂。之后猴子进行了一些列的认知测试。正如研究人员推测的一样,使用了Orexin-A鼻喷剂的猴子与没有被剥夺睡眠的猴子得到的分数一样,这表明鼻喷剂可以帮助它们在睡眠时间较少的情况下保持清醒。而另一组使用安慰剂的猴子则在测试中表现不佳,正如所期待的一样感到很疲惫。
为什么我们现在不往自己的鼻子上喷一喷呢?Orexin-A发生了什么?
Siegel称Orexin-A的研发工作现在还在继续并且进行的很顺利,只是还没有上市。事实上,许多头条新闻都没有提到开发Orexin-A并不是把它作为“睡眠替代剂”,而是让那些具有嗜睡症——患有神经紊乱,阻碍它们调节睡眠周期的人使用的。
Siegel告诉Motherboard,当他看到第一个报道Orexin-A的文章标题时:“很荒缪,我重来没有这么说过,我不认为有药物可以替代睡眠,这是不可能的。”
但是在缓解嗜睡症的临床症状方面,Orexin-A应该算是一种神药:在猴子身上进行的一系列试验,以及在德国嗜睡症患者身上进行的临床试验都证明了这种药物十分有前途。
9年后,嗜睡症患者无法使用Orexin-A,主要还是归结于制药公司和钱。
Siegel说:“需要很多钱来购买这种药物。你还要招募好几百人,并且都要被医生诊断过。”
更重要的是,制药公司无法通过Orexin-A赚很多的钱,因为提取的神经肽促食素这种物质是由大脑自然产生的。同时又因为Siegel已经将他的研究结果发表出来了,生产药物的方法无法被授予专利。
他说:“没有制药公司承诺开发它,因为它不值得人们付出努力。”
同时制药公司生产出了Orexin-A的对立药物:Belsomra。Orexin-A是将兴奋剂固定在大脑的神经末梢上,而Belsomra则是一种相反的药物:阻止这些分子固定在神经末梢上,可以用来治疗失眠症以及睡眠障碍。
Belsomra代替Orexin-A的成功并没有什么秘诀,只是因为这种药物可以挣更多的钱。尽管这种药物有一系列的副作用,包括抑郁和自杀倾向,但它的市场仍是巨大的。美国失眠的人口数远远高于患有嗜睡症的人口数,因此治疗失眠的药物拥有更多的需求。
至于多数新闻标题提到的“代替睡眠”的效果是完全不可能的。Siegel称,虽然服用安非他命是可以做到不用睡觉,但不睡觉会带来十分可怕的后果。Orexin-A不应该这么用,如果这么用的话会带来一系列问题。
他说:“任何试图通过消除睡眠改变大脑平衡的药物都会有类似的效果,促食素也会上瘾,就像鸦片上瘾一样。”
Siegel依旧希望Orexin-A能够被开发,帮助那些嗜睡症患者。
他说:“我希望它被开发。”他补充到,至少有一组研究小组正致力于研究这种药物,但等到它上市还需要好多年。
他说:“我认为它是完全有可能被开发的,因为没有任何一种药物像他一样完美。”

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http://motherboard.vice.com/read/the-nasal-spray-that-was-supposed-to-replace-sleep

The Nasal Spray that Was Supposed to Replace Sleep

If you believed the headlines you read a decade ago, you might have thought that come New Year’s Day in 2016, we’d be wide awake after a night of celebrations, high off the effects of a nasal spray wonder drug that has replaced sleep.

That drug is called Orexin-A, and in 2007 its reveal produced headlines like “Snorting a Brain Chemical Could Replace Sleep” and “DARPA Develops Brain Chemical to Replace Sleep.”

At the time, a study led by UCLA professor Jerry Siegel introduced a "a totally new route for increasing arousal, and the new study shows it to be relatively benign," as he told ABC News at the time. Rumors floated that the drug could become an effective sleep replacement that didn’t have the negative side effects, like addictive properties and mood swings, of its predecessors, like caffeine pills and stimulants or amphetamines, many of which can’t produce positive effects without dragging a slew of problems along with them.

In the study, a group of lab monkeys were deprived of sleep for 30 to 36 hours, and then given either Orexin-A or a placebo. The monkeys were then presented with a series of cognitive tests to complete. As the researchers had suspected, the monkeys who were given Orexin-A nasal spray scored the same as monkeys who were not deprived of sleep, suggesting that the spray may have helped them stay alert on far less sleep. Meanwhile, group given a placebo performed poorly on the tests, as would be expected of a very tired monkey.

“It won't be a perfect drug, but no drug is.”

So why aren’t we all shooting sleep up our noses now? What happened to Orexin-A, the sleep wonder drug?

According to Siegel, work on Orexin-A is still alive and well, though it hasn’t reached shelves yet. In fact, what most of the headlines that heralded the coming of Orexin-A failed to mention is that the drug isn’t really meant to be a “sleep replacement” in the first place. It’s intended for use by narcoleptics, people who suffer from a neurological disorder that prevents them from regulating their sleep-wake cycles.

“It's ridiculous,” Siegel told Motherboard, about the first headlines that came out about Orexin-A. “I certainly never said that. I remember it coming out. There’s no drug that can replace sleep. I don’t think that’s likely—or desirable.”

But in terms of helping ease the symptoms of narcoleptics—meaning, creating a drug that could stave off both sleepiness and catoplexy (sudden physical collapse), Orexin-A could be a godsend: in both Siegel’s monkey trials and in a series of trials on narcoleptics in Germany, the drug showed promising effects.

Still, nine years later, people who suffer from narcolepsy aren’t using Orexin-A. The problem, as it boils down, lies with the pharmaceutical companies and money.

“It takes a lot of money to get a drug,” said Siegel. “You have to enroll hundreds of people, and they all have to be seen by physicians."

What’s more, it’s not likely that a company would make a lot of money off Orexin-A. Because the substance it’s extracted from, the neuropeptide orexin, occurs in naturally in the brain—and because Siegel has already published the results of his study—the drug and its method of administration (snorting) can’t be patented.

“No drug company has undertaken to develop it because it’s not worth their effort,” he said.

Meanwhile, drug companies have developed Orexin-A’s opposite: a sleep aid called Belsomra. While Orexin-A, an agonist, works by binding to receptors in the brain, Belsomra is an antagonist drug: it blocks molecules from binding at those receptors, and can be used to treat symptoms of insomnia, a sleep disorder that can be called the opposite of narcolepsy.

Belsomra succeeded where Orexin-A has not specifically because it can make more money. Even though the drug comes with serious side effects, including depression and suicidal thoughts, its market is huge. The number of people who suffer from insomnia in the US (60 million) is much higher than the number of people who have narcolepsy (200,000), and—excluding the market of college students who want to stay up all night to study for finals—therefore there is much greater demand for insomnia cures.

As for entirely “replacing” sleep, as some of the headlines had originally predicted, that may still be out of reach. According to Siegel, this is already possible with certain amphetamines—but not sleeping has dire effects. Orexin-A shouldn’t be used this way, and would probably cause a host of problems if it was.

“It is likely that any drug radically changing the brain’s balance to eliminate sleep would have similar effects,” he said. “Orexin might also be addictive in the same way that opiates are addictive.”

Still, Siegel hopes that Orexin-A will one day be able to help people with narcolepsy—without some of the negative side effects of existing drugs like Modafinil and Provigil.

“I hope that that it will be developed,” he said, adding that there is at least one research group working on developing a pill form of the drug, but it release is still years away.

“I think it probably will be developed,” he said. “It won't be a perfect drug, but no drug is.”


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