Ecstasy derivative targets blood cancers

October 6, 2011 by Laura Glitsos
PhD student Michael Gandy, who worked on the project and Associate Professor Matthew Piggot. Image: Bob Blucat

(Medical Xpress) -- A team of UWA researchers have found they may be able to alter the club drug ‘ecstasy’ to kill certain types of blood cancers at the same time boosting the potency and reducing the psychoactivity.

School of Biomedical, Biomolecular and Chemical Sciences Associate Professor Matthew Piggott says when the UWA team was researching the use of Methylenedioxymethamphetamine (MDMA) in Parkinson’s disease drug discovery, they came across a paper suggesting it may also be useful in treating blood cancer.

So the UWA scientists collaborated with University of Birmingham Professor John Gordon and his team to increase the toxicity of the drug toward blood cancer cell lines, while decreasing its psychoactive effects.

While MDMA was never marketed as a therapeutic drug, it was discovered as a ‘party drug’ in the late
70s and early 80s mainly due to its ability to induce euphoria.

Now, A/Prof Piggott says MDMA’s structure can be “tinkered with” with to create MDMA analogues (compounds structurally similar to MDMA) that could have improved therapeutic properties.

“Professor Gordon found MDMA to be weakly toxic to certain types of blood cancer cell lines, so he presented the idea of ‘redesigning the designer ’,” he says.

“We contacted him and he was very keen to test our analogues—initially created for Parkinson’s disease treatment research—on his cell lines.

“That’s how it started.”

In order to make the analogues suitable for treatment, the team must focus on removing the psychoactive effect while boosting the toxicity to cancer cells.

To do this, the researchers change some ‘substituents’, particularly the alpha-substituent, in the analogues, much like removing or adding building blocks. The altered structure modifies the biological properties.

“We had some limited anecdotal evidence...because of the work of maverick chemist Alexander Shulgin, who would make different compounds and test them out on himself and his friends,” A/Prof Piggott says.

In terms of increasing its potency against blood cancer cells lines, A/Prof Piggott says it involves “logical trial and error”.

“Initially six compounds were screened but most were not very active. However, there was one that was ten times more potent, and this became the basis for the next batch of analogues,” he says.

“We are currently at the process of making analogues of the best ‘lead’ compound we have discovered so far—which is 100-fold more potent.”

A/Prof Piggott says the compounds are being evaluated using in vitro , but the next step would be testing them in an animal model of .

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not rated yet Oct 06, 2011
I don't understand why it is necessary to remove the euphoric effect for people undergoing chemotherapy. One would think that that would be a benefit.
5 / 5 (3) Oct 06, 2011
Very possibly it is because use of the drug for its euphoric effect is easily habit-forming as euphoria itself is a desirable state of mind for most people, and especially for those enduring constant pain and/or depression.
1 / 5 (1) Oct 06, 2011
I seriously doubt MDMA could be called habit-forming, more like they just don't want people tripping balls during treatment.
1 / 5 (1) Oct 07, 2011
MDMA is not habit forming. I intend to test the hypothesis by using myself as a guinea pig all in the aid of science and the prevention of cancer.
not rated yet Oct 07, 2011
Pretty much anything that makes people feel some sort of positive effect is habbit forming by definition (drinking coffee, smoking, marijuana, eating your favourite cereal in the morning, ect, ect). Some things are addictive (habit forming) or create a dependency to the drug; either way, the affect still applies to MDMA, especialy since they would be in a weakened mental state (at least the majority would be anyways; always an exception) and less resistant to the addictive effects.
5 / 5 (1) Oct 07, 2011
Pretty much anything that makes people feel some sort of positive effect is habbit forming by definition

The problem is not so much the habit but the effects of withdrawal. Eating your favorite cereal might be habit forming but will probably not lead to withdrawal symptoms once you stop.
Using an euphoric stimulant (or merely a painkiller) may very well lead to withdrawal symptoms - and hence dependency.
not rated yet Oct 07, 2011
I agree that the problem is not so much about habit forming. I was just showing that it can indeed be habit forming because of previous posts. Becoming dependant implies habit forming (usually) but that was not point I was trying to make.
5 / 5 (1) Oct 07, 2011
Because the ungodly amounts of morphine they give chemo patients isn't habit forming at all. Better make sure they don't feel all lovey-dovey either.

Damn hippies.
not rated yet Oct 09, 2011
I should think it isn't just the psychoactive effects they are worried about - possibly the neurotoxic effects of any amphetamine derivative?
not rated yet Oct 10, 2011
Euphoric stimulant that may be habbit forming versus DEATH. Perhaps im missing something here.

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