Designer poppies yield better painkillers

Australian scientists have discovered how a naturally morphine-free poppy blocks production of the narcotic, in a finding that could lead to the development of more effective drugs.

The opium poppy is the source of codeine, morphine and other analgesics, as well as opium and heroin. But the mutant poppy known as top1 produces neither morphine nor codeine.

In Thursday's issue of the journal Nature, researchers at the Commonwealth Scientific and Industrial Research Organization in Australia describe how the plant makes precursors of the narcotics, which have been developed into new synthetic analgesics.

“We are already using this knowledge to produce other designer changes in poppies to serve human pharmaceutical needs better,” Dr. Philip Larkin of CSIRO said in an interview. “The new poppy variation can produce, at very high yield, thebaine and oripavine (rather than morphine and codeine). These two alkaloids are preferred starting points for the subsequent manufacture of a new generation of powerful analgesics.”

Alkaloids are organic compounds from plants that are used as drugs.

Treating addiction, too
The drugs derived from the plant include buprenorphine and oxycodone, which are safer and better-tolerated by patients than morphine and codeine. “Buprenorphine and other derivatives of thebaine and oripavine, such as naltrexone, are also playing a major role in treatment of opiate addiction,” Larkin added.

The morphine-free poppy was discovered in 1995 in the Australian state of Tasmania, which grows 40 percent of the world’s legal opiates. It was first sown as a commercial crop in 1997 and now makes up about 40 percent of the entire Tasmanian poppy crop.

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Larkin and his colleagues studied the genetic makeup of the mutated plant and identified differences between it and the opium poppy.

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Genetics plus pharmacology
They found that the mutated plant blocks a biochemical process that would normally produce morphine and codeine and leads to the accumulation of thebaine and oripavine.

“This is a good example of plant genetics working hand-in-glove with drug design/discovery, where not only new drugs are brought to market, but new plants are deployed to do much of the difficult chemistry for us,” said Larkin.

“Plant-based pharmaceuticals are very important, and the genetic revolution will increasingly enable us to develop plants to sustainably and efficiently manufacture new-generation drugs.”