Side-effects study opens up new drug leads

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Scientists have identified possible new targets for existing drugs by comparing their side-effects

Existing drugs could be used to treat a broader range of diseases, according to scientists in Germany and Denmark, who have predicted drug targets by using side-effects data on medication labels.

As well as binding to their intended target, drugs also interact with other proteins in the body triggering side-effects. By comparing chemically dissimilar drugs that have the same side-effects, the team predicted additional targets for 20 pairs of drugs that are already on the market. They tested the effects of nine of these drugs on cultured cells, showing that their predictions were correct.

Peer Bork of the European Molecular Biology Laboratory in Heidelberg, who led the team, explains that their approach could open up the use of old drugs in new therapeutic areas. For example, the team found a link between Prozac (fluoxetine) and the anti-ulcer drug Aciphex (rabeprazole). Both drugs targeted the dopamine receptor D₃ - the primary target of Parkinson’s drug Celance (pergolide).

Prozac and the anti-ulcer drug Aciphex both target the same dopamine receptor as the Parkinson’s drug Celance

The team also found that the antidepressant Remeron (mirtazapine) and insomnia drug Sonata (zaleplon), both interact with the histamine H₁ receptor. Meanwhile, like the antidepressant Effexor (venlafaxine), the Alzheimer’s drug Aricept (donepezil) targets the serotonin transporter - indicating it could also be used to treat depression.

Drug targets are usually determined by a drug’s molecular features and its interaction with cultured cells. Bork explains that the team’s technique can also be extended to other types of drug reaction. For example, the team next plans to study the effects of drug interference in a patient.

Because the drugs identified by the team have already been approved for use once, winning approval for a new indication is likely to be cheaper and faster than for a brand-new drug.

But Oliver Stohlmann, a spokesman for drug firm Pfizer, says that while the research is interesting, the industry already systematically investigates drug side-effects. He notes that many drugs on the market were originally intended for a different use. Pfizer developed Viagra, for example, to treat angina. ’Our aim is to fully understand the biological process, so we can reduce unwanted effects and, in some cases, identify potential new drug targets and new uses,’ Stohlmann adds.

Manisha Lalloo

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