Strange as it may seem, the medicine that broke all sales records was a fluke. At the pharmaceuticals group Pfizer researchers were looking for a new medication for cardiovascular disease. One substance reviewed was sildenafil, the active component of the Viagra pill. There was con­siderable hope that it would be possible to use it to combat chest pains (angina pectoris), but in clinical tests in the 1990s the drug seemed to be a flop. Researchers detected little of the intended effect on the heart and the group saw little hope of a return on its investment. Then, strangely enough, reports came in from test subjects of unforeseen, but

definitely pleasant side-effects. The strength of the drug Viagra lay not in the ribcage, but in the penis: long-lasting, hard erections and more stamina in lovemaking. A number of test subjects flatly refused to re­turn their supply of the drug at the end of the research period and one of them even satisfied his need by breaking into the research lab. It slowly began to dawn on those concerned that with sildenafil the so­lution to a problem affecting men all over the world had fallen into their lap.

Once the desire has been awakened and the stage of foreplay is reached, an erection pill can do its work. Between twenty and 30 min­utes after the drug has been taken the erection-causing action kicks in. How do sildenafil and the more modern PDE5 inhibitors work? With the right mood and in the right circumstances nerve impulses from the brain stimulate the production of cyclic guanosine monophosphate (cgmp) in the penis. As a result the smooth muscle cells of the spongi­form network in the erectile tissue compartments relax. (When the penis is flaccid, the smooth muscle cells are on the contrary taut.) The penis finds rest only in erection, in sex and, for by far the longest peri­ods, each night during rem sleep.

When cgmp is released into the erectile tissue compartments there is a dilation of the arteries, and more blood flows in. At the same time the increasing volume of blood forces the exiting veins shut, retaining blood in the penis and causing an erection.

The enzyme phosphodiesterase 5 (PDE5) breaks down cgmp, so that the erection is not maintained and the blood flows away as fast as it enters. This the point at which PDE5 inhibitors like sildenafil (Viagra), vardenafil (Levitra) and tadalafil (Cialis) help by neutralizing the erec­tion killer phosphodiestarase 5. Cialis has the longer effect, 36 hours, and is also called ‘the weekend pill’, offering the advantage that inter­course does not have to happen soon after taking the pill: one can wait until Saturday or even Sunday – an important consideration, knowing that many women dislike making love to order. PDE5 inhibitors protect cgmp, then, so that blood remains longer in the erectile tissue com­partments. PDE5 inhibitors act not only in the penis, but also in vary­ing degrees in the other pde receptors. By 2007 twelve of these had been identified. The most common side-effects of PDE5 inhibitors are headache, a reddish complexion, a full feeling in the stomach region, a bluish haze in front of the eyes, dizziness and skin rashes. In these loca­tions pde inhibitors with a different number have been pinpointed. The PDE5 inhibitors, for example, act to a minor extent on the pde6 receptors in the retina. In addition it is important that PDE5 inhibitors should not be taken at the same time as medication containing nitrate; this can cause sharp drops in blood pressure. Since 2006 sildenafil has had one other official use: the drug can lower blood pressure in the pul­monary circulation. Raised blood pressure in the blood vessels of the lung is life-threatening and sometimes very difficult to treat.

At the end of 2006 banner headlines announced that British doc­tors had saved the life of a premature baby with Viagra. The doctors administered the drug to a little boy, who at birth weighed only 780 g and was struggling with one non-functioning lung. The medication opened tiny blood vessels in his lungs, allowing oxygen to be absorbed by his blood in spite of this. The parents of baby Lewis, who had been born in August 2006, feared for his life and had even prepared for the funeral – but in December they were able to take him home!

PDE5 inhibitors are registered only for men with erection problems. Studies in women were inconclusive and did not finally result in regis­tration. Female sexual problems tend to be more complicated and con­sist of symptoms that are hard to quantify. PDE5 inhibitors have a salutary effect on men’s minds and perhaps also on their relationships with women, as was maintained by the actor Jack Nicholson in an interview with Playboy in 2004:

Over the years I have heard many people, after ending a mar­riage or a relationship, say, ‘I would never have left her if I could have said, without fear of shattering her entire existence,

‘I just don’t want sex anymore.’ The relationship could have continued if I had been able to say, ‘Fuck someone else if you want.’ Everything would have been fine between us. Instead, the disinterest in sex that can come along becomes so intense that it can dominate the relationship. Viagra solves that. Once, twice a month – and regardless of what people tell you, that’s enough – stimulate yourself with this pharmacological solu­tion, go out there and tear Mom up, baby, and everything is fine. It could save many relationships.