BBC Focus Magazine

[jpYB3Gq]

http://www.abc.net.au/science/articles/ ... 224191.htm

Scientists create new type of painkiller
Monday, 23 May 2011 Clare Pain
ABC
-----------------------------------------------------------------------------

New direction Scientists have found a way to make a molecule, used in traditional Asian medicine, which may lead to a whole new class of pain-killing drugs.

The molecule, conolidine, is one of many complex organic molecules present in a tropical flowering plant used in Chinese, Indian and Thai herbal medicine to fight inflammation and pain.

Unfortunately, only minute quantities of conolidine can be extracted from the plant: nowhere near enough to be able to test its biological properties.

Professor Glenn Micalizio and colleagues at the Scripps Research Institute in the USA set out to synthesise conolidine, starting from a readily available compound known as a pyridine.

The nine-step route that Micalizio's group has designed to make conolidine is described in this week's edition of Nature Chemistry.

The process produces an 18 per cent yield of the chemical, giving the scientists an ample supply to investigate its properties.

No recorded side-effects
The team then tested whether conolidine had an effect on pain by carrying out accepted studies on laboratory rats. Their results showed it to be a very effective analgesic - almost as effective as morphine.

Morphine and other opioid analgesics provide the best pain relief, but there are serious and unpleasant side effects including addiction, nausea, depression of breathing and constipation.

Opioid painkillers act on cells in the brain, whilst other pain-killers like paracetamol and ibuprofen act peripherally, at the site of the damage.

Interestingly, the scientists were able to show that conolidine does not act in the same way as opiates such as morphine. "Conolidine is a very potent analgesic", says Micalizio, "but it is not an opiate. It doesn't bind to the opioid receptors".

This fits with the behaviour of the rats on conolidine. They seemed to experience no side effects. "The rats aren't high and they are functioning well - it sounds like a good starting point for an analgesic", comments Micalizio.

The researchers now want to understand how conolidine works. So far the scientists have tested 55 different receptor molecules that they thought might bind conolidine - all with no success. "We're still looking", says Micalizio.

He thinks that, like morphine, conolidine may be acting directly on the brain, but using different receptors.

"What's amazing", he says, "is that when we give the rats conolidine the concentration in their brains is higher than in their blood plasma. This is a brain-penetrant small molecule"

'Significant potential'
Professor Basil Roufogalis of the University of Sydney's Faculty of Pharmacy, says there has been intense research by pharmaceutical companies over the past few years to develop new drugs to relieve pain, but progress has been disappointing.

"This new molecule has significant potential for an area of pain that is currently poorly controlled," says Roufogalis.

"The next steps are to see if it is active in humans, preferably by the oral route, and also that it is free of serious side effects."

"The preliminary results suggest that undertaking this next phase of research should be feasible and potentially important for non-opioid pain treatment."

Micalizio is now seeking to partner with a pharmaceutical company to help him push the program forward.

[Healerman]

Given the present state of me sciatica, bring it on.

[M Paul Lloyd]

I'll trade you your sciatica for a dodgy hip and four teeth that need extracting.