As Nicola Mondaini, Urologist at Santa Maria Annunziata Hospital of Florence and National counselor of Italian Andrology Society, told to Pharmaworld Magazine: «There already are several generics manufacturers that are prepared for the opening of this field in Italy. To my knowledge, everything is ready and during next June or July we will find the generic version of Sildenafil across Italian pharmacies».
According to European Medicine Agency website three manufacturers have been recommended by EMA and then Authorized by European Commission to commercialize Sildenafil: Teva (in November 2009), Ratiopharm (in December 2009) and Actavis (in December 2009).
«Sildenafil debut on generics market – said Nicola Mondaini – will somehow have an effect also on the world of other drugs for erectile dysfunctions. It will most likely impact on Levitra (Vardenifil) that has a pretty similar mode of action. Maybe it will also affect Cialis (Tadalafil) in some extent but, since this drug has a different half-life and a brand new indication also on the symptoms derived from Benign Prostatic Hyperplasia I do not think that the group of people that assume this Cialis will be suggested to change toward generic Sildenafil».
How the “blue pill” works
Sildenafil citrate, sold as Viagra and under various other trade names, is a Pfizer’s drug used to treat erectile dysfunction and pulmonary arterial hypertension (PAH). The mechanism of action of Sildenafil involves the protection of cyclic guanosine monophosphate (cGMP) from degradation by cGMP-specific phosphodiesterase type 5 (PDE5) in the corpus cavernosum. Nitric oxide (NO) in the corpus cavernosum of the penis binds to guanylate cyclase receptors, which results in increased levels of cGMP, leading to smooth muscle relaxation (vasodilation) of the intimal cushions of the helicine arteries. This smooth muscle relaxation leads to vasodilation and increased inflow of blood into the spongy tissue of the penis, causing an erection. Sildenafil is a potent and selective inhibitor of cGMP-specific phosphodiesterase type 5 (PDE5), which is responsible for degradation of cGMP in the corpus cavernosum of penis. The molecular structure of Sildenafil is similar to that of cGMP and acts as a competitive binding agent of PDE5, resulting in more cGMP and better erections. Without sexual stimulation, and therefore lack of activation of the NO/cGMP system, Sildenafil should not cause an erection. Other drugs that operate by the same mechanism include Tadalafil (Cialis) and Vardenafil (Levitra).
As commented by Dr. Mondaini: «The discovery that Sildenafil has a function on erectile dysfunction was quite serendipitous. In fact this molecule was studied by researchers with the aim to find a solution to the problems given by nitrates. These drugs are indicated in cardiologic problems but have a short half-life. So the idea was to find something that lasted more and Sildenafil was one of them. Unfortunately this drug revealed little results in the field of vasoactive drugs for heart problems, but it surprisingly had very interesting effects on the erection».
HISTORY OF A LOVE DISCOVERY
Sildenafil (compound UK-92,480) was synthesized by a group of pharmaceutical chemists working at Pfizer’s Sandwich, Kent, research facility in England. It was initially studied for use in hypertension (high blood pressure) and angina pectoris (a symptom of ischemic heart disease). Phase I clinical trials suggested that the drug had little effect on angina, but that it could induce marked penile erections. Pfizer therefore decided to market it for erectile dysfunction, rather than for angina. The drug was patented in 1996, approved for use in erectile dysfunction by Food and Drug Administration on March 27, 1998, becoming the first oral treatment approved to treat erectile dysfunction in the United States. It soon became a great success: annual sales of Viagra peaked in 2008 at US$1,934 million.