Viagra

Viagra can you perk up… no, not what you think.

Rejoice all ye travelers: Viagra will perk you up and shorten your jet lag if you go from West to East.

How does it work?

 

The biological clock

This concept needs no introduction: Most animals gear their activities to the light-dark (LD) cycles. In mammals, this “biological clock” resides in a specific area of the brain, called the suprachiasmatic nuclei (SCN). The principal signal that adjusts the biological clock with the environment is the LD cycle.

But how does an area deep inside the brain sense light? Of course, you would say. Don’t we have an optic nerve that transmits images from the retina to the brain? But, if that were the mechanism, blind people would not have been entrained (synchronized) to the LD cycle; but, they are. They go to sleep at night and wake up in the morning just like seeing people.

There is a bundle of nerves that goes from the retina to the SCN called the retino-hypothalamic tract. It has no function in vision; its sole function is to transmit a signal to the SCN saying “it’s light outside”. What happens next is quite complicated but basically, this nerve causes the release of neurotransmitters (glutamate and PACAP), which initiate a signal transduction cascade in SCN neurons that ultimately results in a phase shift of the circadian system.

Why do we need a phase shift? Imagine that we were subjected to an eternal darkness. Then our biological clock would function at its own internal rhythm (“free running”), unaffected by light-dark. If you did this experiment on yourself, you’d find out that your internal clock runs a bit slower than a 24-hour clock; every morning you’d sleep a bit later until your “day” reached 28 hours. Obviously, there is a need to adjust this internal clock to the phases of night and day (hence, “circadian rhythm”, circa=around, dia=day). This adjustment is accomplished by a system of neuronal chemical messengers that synchronize the clock by inducing phase delays during the early night and phase advances during the late night. The pathway we are dealing with today is known to be involved in phase advances but not phase delays. That’s exactly the action needed if you need to adjust your circadian rhythm going from say, New York to London, because London is ahead by 5 hours.

One of the important molecules participating in this system is called cGMP. cGMP has a natural enemy: An enzyme called PDE5 (phosphodiesterase 5) that hydrolyzes it and destroys its action. Thus, inhibiting PDE5 should increase the levels of cGMP, and thereby potentiate the phase advance of the circadian rhythm.

 

What does all this have to do with Viagra?

Well, as luck, or fate, would have it, cGMP, which is a vasodilator, is also critical for, you guessed it, penile erection. And Viagra, or sildenafil for the cognoscenti, works by inhibiting PDE5.

 

The obvious experiment

So it was only a question of time before somebody would see if the inhibitor of PDE5 in the penis would work on the same enzyme in the brain. Sure enough, it did. Giving Viagra to hamsters that had been kept in their normal LD cycle and then subjected to an LD cycle that was advanced by 6 hours (same as a jet lag going from N.Y. to Paris ), shortened their entrainment from 12 days to 9 days.

Of course, this experiment was done in hamsters, and they don’t frequently travel across time zones. But the biochemistry and neurophysiology of the circadian rhythm are the same as our, and it is just a question of time before such an experiment is carried out in humans. Are we going to see ad campaigns by the airlines touting free Viagra for premium travelers, ostensibly to combat jet lag? But closer to home: Moving the clock one hour forward for daylight savings time is the equivalent of travel across one time zone. Hmmm… Viagra may make the loss of an hour sleep a lot easier to take.

 

And for dessert…

This is from the Times of London:

“Israeli fighter pilots may soon be receiving Viagra-style pills to help them to perform better at greater heights, according to a study by military officials released yesterday.

…The proposal, to be presented to the air force by a retired general, developed from a study by Israeli doctors among mountain climbers scaling Mount Kilimanjaro in Tanzania, according to Bamahaneh (‘On the Army Base’), an official military magazine. The study found that tadalafil, the active ingredient in Cialis, a Viagra-like anti-impotence drug, helped climbers to ward off fatigue and dizziness at greater heights.

With combat pilots operating hi-tech equipment in low-pressure environments, doctors believe the drug could enhance their operational abilities.

‘The Viagra family of drugs is considered effective in these conditions because when there is a long shortage in oxygen, it leads to high blood pressure in the lungs, and the drugs help fight that,’ a military medical officer told the weekly magazine.

Israeli air force pilots are sometimes called upon to perform incredible feats of airmanship, such as the 1981 operation to destroy Iraq’s nascent nuclear reactor. Eight F16 fighter-bombers, escorted by six F15 tactical fighters, flew almost 700 miles (1,100km) across Jordanian, Saudi Arabian, and Iraqi airspace to destroy the French-built reactor.

According to some accounts, the jets flew in such close formation that any radar pickup would have identified them as one large passenger aircraft.”

Well…with Viagra on board, this air force and its skilled pilots must be truly potent!

Dov Michaeli, MD, PhD
Dov Michaeli, MD, PhD loves to write about the brain and human behavior as well as translate complicated basic science concepts into entertainment for the rest of us. He was a professor at the University of California San Francisco before leaving to enter the world of biotech. He served as the Chief Medical Officer of biotech companies, including Aphton Corporation. He also founded and served as the CEO of Madah Medica, an early stage biotech company developing products to improve post-surgical pain control. He is now retired and enjoys working out, following the stock market, travelling the world, and, of course, writing for TDWI.

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