Researchers may have discovered why the popular antimalarial, quinine, causes debilitating side-effects.
Tryptophan, an essential amino acid in the human diet, appears to be the key.
Quinine is known to cause nausea, blurred vision and hallucinations, but until now no one has been able to explain these side-effects.
Writing in the Journal of Biological Chemistry (3 July), scientists from the University of Nottingham in the United Kingdom suggest quinine may block the transport of tryptophan into cells because it has a similar chemical structure to the amino acid.
Richard Pleass, study co-author and associate professor at the University of Nottingham's Institute of Genetics, explains that one of tryptophan's functions is to be converted into serotonin — a neurotransmitter that affects mood.
"It doesn't take a leap of faith to see that quinine could interfere with serotonin's capacity to affect mood in humans, causing some of the side effects we see with quinine — like hallucinations," he says.
It follows that people who take quinine when their bodies are already running on relatively low levels of tryptophan are at risk of experiencing the most serious adverse reactions, says Simon Avery, study co-author and associate professor at Nottingham University's School of Biology.
"Variations in tryptophan levels in people could potentially determine whether they're going to experience adverse effects from quinine or not," he told SciDev.Net.
Avery's team studied yeast cells which, like human cells, need tryptophan. Yeast can absorb tryptophan from its environment but, unlike humans, it can usually also make its own. The team found that yeast cells lacking the gene for synthesising tryptophan were extremely susceptible to quinine poisoning.
While some foods are rich in tryptophan, others, such as yam — a popular staple in Africa — are tryptophan-deficient. The authors write that diets poor in tryptophan are common in undernourished populations.
Following human trials, the study's results could point to tryptophan supplements being used as a simple preventive to some or all of quinine's side-effects. But for now the researchers warn against taking tryptophan supplements to counter the drug's side-effects.
"We don't know yet how tryptophan affects quinine's interaction with the malaria parasite," says Avery. "It's quite possible that tryptophan could suppress the side effects of quinine but at the same time it might block quinine's action against the parasite."
Quinine was first used to treat malaria in the early 17th century and remains a commonly used antimalarial drug.
Journal of Biological Chemistry 284, 17968 (2009)