C22H30N6O4S - a Wonder Pill!?!
(June 1st 2007) Sildenafil is well on the way to becoming a blockbuster. It is not only used to overcome erectile dysfunction but since the beginning of this year, it has also been used as a therapy for pulmonary hypertension. Now Argentinean scientists have reported that it also helps golden hamsters to recover from jet lag! The most serious side effect observed was - wait for it ... calls to Karin Hollricher!
In the 80's Pfizer tested a chemical substance with the chemical formula C
22H
30N
6O
4S as a remedy for cardiovascular diseases. The substance called Sildenafil has turned out to be a real bomb. Quite by accident, it was noted to be effective in treating erectile dysfunction and it wasn't at all surprising that Sildenafil became a top seller overnight. Since 1998 Pfizer has been selling it in the form of little blue pills under the brand name Viagra®. So you don't suspect us of plugging Viagra®, we'd like to mention that two other similar compounds have since been brought onto market, Taladafil (brand name Cialis®) and Vardenafil (brand names Levitra® and Vivanza®).
Sildenafil has turned out to be an eclectic drug. German researchers tested the blue pills in the Himalayas. Certainly not for its arousing effects but for its potential impact on the lung. On top of Mount Everest, more than 5000 meters high, they proved that Sildenafil eases breathing by constricting lung vessels. That not only enhances the performance of mountaineers but today also helps patients suffering from pulmonary hypertension.
All these effects are provoked by the inhibition of the enzyme phosphodiesterase 5 (PDE5). PDE normally leads to a decrease in cellular cGMP. This second messenger is known to be involved not only in the relaxation of smooth muscles but also in the regulation of the day-night rhythm in hamsters. cGMP levels in the rodents' brains exhibit daily and circadian variations with maximum values during the day. This variation seems to be mainly due to changes in PDE activity. That's why Patricia V. Agostino and her colleagues in Buenos Aires tested whether the many-sided pill has any effect on the circadian rhythm in hamsters. They injected hamsters with low concentrations of Sildenafil at night, before turning on bright lights six hours early. They then observed how the hamsters adjusted to the change, by noting how soon they began running in their exercise wheels. With Viagra the animals adapted to the change of night-day rhythm 25 to 50 per cent more quickly than control hamsters.
However, the anti-jet-lag remedy worked only when applied before an advance in the light/dark cycle - it could not prolong the night. Scientists believe that Viagra and its sister drugs could be useful for frequent flyers travelling east and shift workers. It is important to tune the dose very accurately. Hamsters, for instance, coped with jet lag best at 10 mg Sildenafil per kg in weight but that same dose also caused a permanent erection... which could be quite annoying (not to mention frustrating) if you are sandwiched between two strangers in the oppressive narrow chair of a claustrophobic aircraft.
