History of PDE5 Inhibitors. Annals of Sexual Medicine

A phosphodiesterase type 5 inhibitor (also called PDE5 inhibitor) acts by suppressing the degradative impact of PDE5 isoenzyme which it has on cyclic GMP in smooth musculature, which line blood vessels, supplying numerous tissues. Two bodies of the penile organ are dilated under the action of this drug. Consequently, sexual excitation is facilitated and a good erection takes place. That is why the meds of this class are commonly used for treating erectile dysfunction (sometimes referred to as impotence, and often used in everyday speech simply as ED). Revealing PDE5 inhibitors’ efficacy and their applicability for handling ED is considered a remarkable case. Before its discovery only intracavernosal injection and penile implant were used for combating problems with erection. Invasive drugs and injections don't seem to be attractive remedies for patients. Physicians stated that the small percentage of users experienced significant benefits from them.

Historical Background

When the nitric oxide (NO) was discovered in 1986 (and the Noble Prize was given for this) the new era of the drugs' creation begun.

It was the beginning of the new inventions in this sphere. NO functions as a mediator in various psychological systems. It is engaged in some conditions (of physiological and pathological nature) by creation of the special messenger substance cGMP. Vasodilation impact of NO, which depends on cGMP plays a huge role in optimizing systemic and pulmonary pressures. It maintains good erection, prevents atherosclerotic changes, provides a favorable cardiac effect. PDE5 is the principal isoenzyme, which participates in the cGMP's functioning termination.

The turning point of the discovery of meds was the selection of PDE5i substances which were aimed to become highly demanded on the market. The invention of compound UK-92,480, which is now called sildenafil citrate, indicated the beginning of the PDE5 inhibitors' history. It was discovered and tested for the first time in Pfizer's laboratories.

Sildenafil (Viagra; Pfizer, New York, USA) is the first approved for treating ED PDE5 inhibitor. It happened in 1998 in America and in 1999 in Taiwan. Tadalafil (Cialis; Lilly ICOS, Indiana, USA) as well as vardenafil (Levitra; Bayer AG, Leverkusen, Germany) were officially recognized in most countries worldwide in 2003. Therapeutic approach which includes PDE5 inhibitors features many advantages. Pills are easy in administration and often show high effectiveness. Moreover, side effects are minimal. It makes them the revolutionary remedies for treating problems with erection.

Some Interesting Facts

Francis and Corbin firstly discovered PDE type 5 in 1980. This naturally occurring substance is present in cavernous bodies in big quantities. In 1991, the clinical studies of the sildenafil citrate 50 mg (taken 3 times per day) begun. It happened in England. However, the effect was not visible. Scientists noticed the side effect in the form of the increased erection. It made them think about PDE5 and cGMP as about potent anti ED remedies. According to internationally adopted questionnaires, the efficiency of the therapy based on PDE-5 inhibitors, is 65%-75% (for good intercourse) and 80%-85% (for increased erection).

Additional Uses and Perspectives

Presence of the PDE5 in the arteries’ walls in lungs allows active constituents of the mentioned pills to dilate those vessels. These substances are approved by FDA for treating increased blood pressure in the lung arteries. Additionally, specialists state about its benefits in treating cardiovascular disorders.

In different doses, sildenafil / tadalafil minimized isolated bladder's and urethral contraction, along with prostate strips (studies were conducted on animals). Also, scientists noted that the improvements with lower urinary tract symptoms (LUTSs) took place. But only tadalafil (taken for 5 mg per day) is officially recognized for the treating of LUTSs.

Another aspect of potential use is as follows. Altitude sickness can manifest through 3 main syndromes: severe mountain sickness, high-altitude cerebral edema, high-altitude pulmonary edema (HAPE). The recent researches confirmed that sildenafil and tadalafil can rapidly reduce the symptoms of HAPE.

Read a related article: Use of Tadalafil for Pulmonary Hypertension

Conclusion

To sum up, PDE5i meds are considered the most widespread form of dealing with erectile dysfunctions. They’re akin to NSAIDs in treating pain. They were scrupulously discovered and are frequently studied. So new methods as well as new doses are revealed and more flexible approaches in treatment are applied. The result is great: satisfied patients.