Contact: to feature here

Thread Rating:
  • 0 Vote(s) - 0 Average
  • 1
  • 2
  • 3
  • 4
  • 5
Introduction on Drug Repositioning (with examples)
Drug market is huge. There’s already ~95 000 publically available drugs. Drug development process is long (10-15 years) and it is expensive. A lot of potential candidates are eliminated in the preclinical stages. Even if drug enter clinical trial, it’s not a guarantee that it will be marketed (1 out of 10 drugs complete clinical investigation successfully). Despite having marketed a lot of drugs, pharmaceutical industry still needs to find solution for the long list of disorders.

Drug repositioning is relatively new field in pharmacology that is focused on discoveries of new indications and molecular targets that could be cured using already known drugs. Cases of drug repositioning were noted in the past when new drug indications were accidentally noted during clinical trials. Today, drug repositioning is completely new branch in pharmaceutical industry; large companies have separate divisions (known as “Indication discovery unit” in Pfizer and Novartis or “Common mechanism research” in Bayer) that are dealing with this issue.

Drug repositioning is popular for many reasons. It saves money (probably most important factor in pharmaceutical industry). Over billion dollars and a lot of time and effort are invested in drug development but there’s no guarantee that drug will reach market and be successfully used at the end. There’s always a chance that drug wouldn’t be safe or effective enough to bring invested money back. Also, drug could easily be excluded from the market if some unexpected side effects appear. Other negative aspect of drug development is that it lasts between 10 and 15 years - sick people don’t have that much time to wait for new medicine to appear. And finally, drugs that are proved ineffective for one disorder, but effective for some other, could be applied immediately because evaluation of drug's safety is already finished.

Viagra is one of the most famous examples of drug repositioning. Sildenafil (generic name) is initially developed for pulmonary hypertension and angina pectoris. Erection was side effect noted in all male participants in the study. Scientists recognized the values of the newly detected side effect and Sildenafil (under brand name Viagra) soon became first marketed drug indicated for erectile dysfunction in men. Viagra is on the market from 1998. and it’s still highly profitable (selling profit exceeded 1,9 million dollars in 2008). Successful switch of indications is made thanks to Viagra's mechanism of action. It is PDE5 (cGMP-specific phosphodiesterase type 5) inhibitor. PDE5 degrades cGMP in penile corpus cavernosum tissue. When PDE5 actions is prevented, increased cGMP level result in smooth vascular muscle relaxation and increased blood flow to the penile sponge tissue resulting in erection. Sildenafil was initially designed to prevent pulmonary arterial hypertension by increasing cGMP level that will decrease pulmonary arterial resistance and induce pulmonary arterial wall relaxation. Biochemical "collision" in two seemingly distant organic disorders lays in the fact that PDE5 is distributed within the arterial wall of the lungs and penis exclusively (vasodilatation is not induced in the rest of the body). It turned out that drug is more effective in penis than in lungs and soon enough it was repurposed.

Few more examples on drug repositioning:

Buprenorphine is developed as anti-analgesic in 1980s. In 2002, list of indications was expanded and today it’s almost exclusively used in treatment of drug addiction (for detoxification and long term replacement therapy).

Requip is initially designed as medicine for Parkinson disease. List of additional indications expanded later and now it’s used in treatment of restless leg syndrome and in the treatment of SSRI-induced erectile dysfunction.

Colesevelam was developed as LDL-C lowering agent for the patients with primary hyperlipidemia. Today, it can also be used in patients with type 2 diabetes to improve their glycemic control.

Gabapentin is initially designed as medicine that could treat epilepsy, but it was soon discovered that it’s more efficient in treatment of anxiety disorder.

Examples of drug repositioning are numerous. “Repositioning” approach has few advantages over classic drug discovery process. Whole idea behind drug repositioning is to find alternative indications for the already marketed drugs or drugs that are rejected due to low efficiency rate or more side effects than expected (dose reduction is also an option). Keeping in mind that the number of marketed drugs is incredibly high, it’s just a matter of time when new treatment options for the severe medical conditions will be “reinvented”.
Like Post Reply
Good post. I just stumbled upon your blog and wanted to say that I have really enjoyed reading your posts. I’ll be subscribing and visiting often.
Like Post Reply

Possibly Related Threads…
Last Post

Users browsing this thread:
1 Guest(s)

Introduction on Drug Repositioning (with examples)00