Tadalafil is a phosphodiesterase inhibitor of type 5, which is used to treat erectile dysfunction.
After the great success of sildenafil (Viagra ®) in treating erectile dysfunction, other pharmaceutical companies also began looking for type 5 phosodiesterase inhibitors.
History of the discovery of tadalafil
The tadalafil molecule was discovered by the then pharmaceutical company Glaxo Wellcome (now GlaxoSmithKline) in collaboration with the biotechnology company ICOS Corporation, a collaboration that began in August 1991 with the aim of developing new drugs. Thus, in 1993 the biotechnology company ICOS Corporation began the study of a new compound called IC351, which exhibited inhibitory properties towards phosphodiesterase type 5; although the researchers were not looking for a drug to treat erectile dysfunction in compound IC351, they did recognize a potential drug candidate in that compound.
In 1994, ICOS Corporation researchers requested and obtained a patent for compound IC351, a compound that is structurally different from other phosphodiesterase type 5 inhibitors; finally, in 1995 the first phase of clinical trials began. Despite the fact that the pharmaceutical company Glaxo Wellcome and the ICOS Corporation had an agreement to divide at par, that is 50/50, the gains they would get from the sale of the drugs, in 1996 Glaxo Wellcome let the agreement expire, declaring that the drugs they were developing they were not part of the marketing program of the house itself. The ICOS Corporation, however, continues the development of tadalafil, and in 1997 began the second phase of clinical trials, which was conducted on patients suffering from erectile dysfunction, followed by the third phase of clinical trials, a very important phase that has provided all the necessary evidence to request the Food and Drug Administration to approve and authorize the marketing of tadalafil for the treatment of erectile dysfunction. Thus, on November 21, 2003, the FDA gave permission to market tadalafil.
In order to develop and eventually market tadalafil, in 1998 ICOS Corporation. in collaboration with the pharmaceutical company Eli Lilly and Company. founded Lilly ICOS, LLC, a joint venture company. Thus, in 2003 Lilly ICOS LLC started selling tadalafil under the registered name of Cialis ® first in the United States and then in Europe.
In 2007 the pharmaceutical company Eli Lilly and Company bought the ICOS Corporation for 2.3 billion dollars, and after putting an end to all the operations of the ICOS Corporation, it also ended Lilly ICOS LLC, firing most of the employees of the ICOS Corporation. Only a hundred employees of the ICOS biological section, which was bought by another pharmaceutical company, were saved from the dismissal.
A curiosity about the trade name of tadalafil, Cialis, is that in the United States this term is also a surname of people, so after the marketing of tadalafil many people called Cialis wrote protests to Eli Lilly and Company, claiming that the company changed the name of the drug; however, the company refused, responding that the name of Cialis has nothing to do with the surname of those people.
In May 2009, tadalafil was approved in the United States for the treatment of pulmonary hypertension, while in other countries the evaluation process for tadalafil for this medical application has not yet been completed. A few months before tadalafil obtained approval in the United States, in November 2008, the pharmaceutical company Eli Lilly and Company sold the US marketing rights for tadalafil in order to treat pulmonary arterial hypertension at a another company called United Therapeutics, for the sum of 150 million dollars. In October 2011, however, the Food and Drug Administration approved the use of tadalafil in the United States for the treatment of symptoms of benign prostatic hyperplasia (BPH).
Action mechanism
Tadalafil, like other phosphodiesterase type 5 inhibitors, also needs sexual stimulation to function. The physiological mechanism responsible for the penile erection process includes the release of a certain amount of nitrogen oxide (NO, a molecular "messenger"), in the cavernous body of the penis during sexual stimulation.
Shortly before the FDA approved the marketing of tadalafil, in May 2002, Lilly ICOS presented to the American Society of Urologists a clinical study that showed that the half-life of tadalafil is about 17.5 hours, a much longer half-life than other phosphodiesterase type 5 inhibitors. The same study confirmed that the duration of the effect of tadalafil was even longer than its half-life, reaching even more than 36 hours. Due to such an extended duration of pharmacological action, tadalafil (Cialis) was given the nickname of the "weekend pill".
Even the tadalafil (Cialis) has conquered all the internet pages, most of which offer a very simple way to get the drug, even offering to send the drug to the home of the customer concerned. Many people are tempted to get tadalafil through the internet, seduced by the seemingly low prices and the desire to solve their problem without contacting the doctor, thus bypassing the possible embarrassment in exposing their problem to the attending physician; this is obviously an absolutely wrong behavior, because the doctor is indispensable in the evaluation of the problem, which can be of a different nature and make the use of Cialis useless or even dangerous. In addition, people who are older or have cardiovascular problems should undergo a rigorous preventive medical check-up to make sure that the administration of tadalafil does not lead to any serious side effects or that it does not interfere with the patient's clinical picture.
