Since time immemorial, male impotence was an issue that has been subject of countless debates and has undermined the complexity of the man-woman relationship. Erectile dysfunction (ED) represents a significant part of male impotence. It is estimated that 10 per cent men suffer from erectile dysfunction, and this figure is as much as over 50 per cent for men between 40 and 70 years old.
Viagra, chemically known as sildenafil citrate, was approved by the US FDA on March 27, 1998, as a therapy for erectile dysfunction. The introduction of this drug for the first time offered hope for men, who are suffering from erectile dysfunction. The drug became a blockbuster overnight. The drug's ability to arouse a man was hyped up by the print and electronic media worldwide.
Historical development
The viagra drug research, nonetheless, was not originally intended to produce a male impotence drug. Instead, Pfizer scientists were striving to develop the antihypertensive ability of the drug and a therapy for angina pectoris in men. While screening the drug, researchers at Pfizer laboratory noticed that the drug did not help angina sufferers. But some of the men in the phase I trial reported an increased tendency to get erections. The Pfizer scientists, therefore, shifted their research focus on use of the drug from angina to erectile dysfunction. And viagra was patented in 1996, approved for use in erectile dysfunction by US FDA in 1998 and the drug entered the US market later that year. Thereafter the drug was introduced gradullay on the world market. Within few years, several trade named products (Penegra, edegra, caverta, niagra) were marketed in India by different pharmaceutical manufacturers. The success of viagra could me measured by judging the innumerable number of web sites from which the drug could be bought. Using exact phrase 'viagra' on google search produces 73.3 million websites within 15 seconds. The drug is formulated in a blue, rounded-diamond shaped with film coating. The name viagra has become so popular that anything aphrodisiac is called viagra including herbal viagra and ayurvedic viagra.
The synthesis of sildenafil citrate was first reported in the Bioorganic and Medicinal Chemistry Letters (Vol 6, pp. 1819-1824, 1996). Sildenafil citrate is a synthetic heterocyclic piperazine derivative that acts by selective inhibition of cyclic guanosine monophosphate (cGMP) specific phosphodiesterase type 5 (PDE5) allowing a relaxation of smooth muscles and inflow of blood to the corpus cavernosum, a condition that leads to erection during sexual stimulation. Sildenafil citrate is a potent and highly selective inhibitor of PDE5. The drug's psychological mechanism is being studied by many researchers. Clearly there are two schools of thought. One group thinks that psychological causes including strained relationships cannot be successful with viagra. On the contrary, it will help the impotency resulting from physical causes.
Several side effects of sildenafil citrate were reported during post marketing surveillance. Of the most talked about are serious cardiovascular events, including cardiac sudden death. However, according to extensive data available to date, the drug has been shown to pose minimal cardiovascular risks to healthy people. Many pharmacologists claim that for occasional use in healthy adults viagra is relatively safe. Viagra combined with nitrates, may be lethal and must be avoided.
Erectile dysfunction drugs
Viagra is responsible for the formation of sexual medicine, a new area in medical practice. With its high commercial success, two other erectile dysfunction drugs - tadalafil (cialis, marketed by Eli Lilly & Co.) and vardenafil (Bayer pharmaceutical's levitra) - have been approved by US FDA. Recently, udenafil (called zydena), a new erectile dysfunction drug, has received marketing approval in Korea. Tadalafil, vardenafil and udenafil are also PDE5 inhibitors.
Medical uses of viagra
The drug for treating impotence is customarily called 'lifestyle drugs', simply because impotence is not regarded as a threat to health. Other lifestyle roles of sildenafil citrate like therapy for premature ejaculation and female sexual performance are garnering a lot of attention by the pharmaceutical giants.
However, the drug has potential new applications that could give viagra lifesaving roles. Various studies are underway to this effect. In June 2005, US FDA approved viagra's maker, Pfizer, to market sildenafil citrate (called revatio) as a treatment for pulmonary arterial hypertension (PAH), a rare life shortening vascular disease. Various research teams, many of them supported by multinational pharmaceutical companies in the west, are evaluating sildenafil citrate against cardiovascular diseases. Many scientists are exploring it in liver disease conditions and complications of pregnancy. Since viagra increases blood flow, it might offer some benefits in augmenting sexual functioning in women.
Very recently sildenafil citrate has come to the fore, as the media across the globe reported viagra may help jet lagged travellers. Researchers at Argentina's National University injected viagra to hamsters and made to feel like rodent globetrotters. Adult male hamsters, which were given viagra recovered from jet lag up to 50 per cent faster than hamsters receiving placebo, reported in the proceedings of the national academy of sciences. Scientists are optimistic that a dose of viagra may one day help sift workers and multiple time zone travellers adapt their normal sleep cycles. Viagra interferes with an enzyme that lowers levels of a naturally occurring substance that plays an important role in the regulation of the circadian cycle. Therefore, viagra could be useful in other circadian rhythm disorders.
(The author is reader in pharmacy, Annamalai University, Annamalainagar, Tamil Nadu)