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Overdose Patients can Be Helped by Cocaine 'flush'

by Rajashri on August 29, 2008 at 4:47 PM
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 Overdose Patients can Be Helped by Cocaine 'flush'

A molecule that can help flush cocaine overdose out of the body, before it causes any irreparable damage to the central nervous system has been developed by US researchers.

This advancement results from a study conducted at the University of Kentucky in Lexington.

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The chemists associated with the work have revealed that they created the new molecule by modifying a naturally occurring enzyme.

If the enzyme works in humans, they say, it would be the first therapy to remove the drug from a user's body.

Doctors presently relieve the symptoms of a cocaine overdose by lowering a patient's temperature and reducing his/her heart rate.
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"When patients go to the emergency room, the doctors really can't help a lot. The cocaine is still in their system," says Chang-Guo Zhan, one of the researchers behind this work.

Normally, enzymes in the body combine cocaine with water, and break it down into two harmless products over a sequence of reaction steps.

However, the process is so slow that it takes about 90 minutes to dispose of tiny doses, and much longer for a large overdose.

Zhan claims that the molecule his team has made can break down cocaine much faster.

During the study, He and his colleagues calculated the energy required to perform each reaction step, which enabled them to determine how much energy a molecule should have to successfully react.

Using computer simulations that systematically tweak the structure of the enzyme and predict the effect of these tweaks on the energy barrier, the researchers arrived at a candidate molecule that promised to speed up the reaction by 2000 times.

The researchers then synthesised the molecule, and tested whether it might work in the body.

As part of the study, a highly toxic dose of cocaine was given to 18 mice, of whom 12 had been injected with the modified enzyme.

The researchers found that all of the mice that had received the modified enzyme survived, with only two suffering seizures.

The six controls, which did not receive the enzyme, died.

Zhan believes that this therapy should have few side effects in humans because only five of the 574 amino acids, which make up the enzyme, are changed to modify it.

Pharmacologist Stewart Paterson of King's College London describes the therapy as "promising", but points out that its effectiveness would depend on how quickly it was taken after the overdose.

He says that the team also need to be sure that it does not also break down beneficial compounds in the patient's body.

The study has been described in a paper published in the Journal of the American Chemical Society.

Source: ANI
RAS/M
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