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According to the London Toxicology Group, there has been a seizure in the UK of about 25,000 tablets containing 4-methylthioamphetamine (4-MTA). It is believed that these were aimed at the ecstasy market.

In a press release today the National Criminal Intelligence Service said that pills sold as 'Flatliners' contained 4-MTA.

4-MTA originated from research conducted by Professor Dave Nichols of Purdue University. There is little experimental data on its effects but it has been linked to one death in Holland and two in the UK (in at least one of the cases a number of other drugs had also been consumed). The cause of death may well have been serotoninergic syndrome as 4-MTA is a potent 5-HT releaser and also a monoamine oxidise inhibitor.

Professor Nichols has said of 4-MTA:

"We had been looking for drugs that cause the release of neuronal serotonin,with the expectation that they might have therapeutic value similar to the SSRIs. We had noted that selectivity for the 5-HT uptake carrier seemed to be increased when amphetamine structures had large, hydrophobic groups in the 4-position. A methylthio group falls into this category.

Methylthioamphetamine was readily synthesised and when tested was a very potent releaser of 5-HT. We also then discovered that MTA is a fairly potent inhibitor of MAO-A, which no doubt contributes to the toxic effect. I suspect that the toxicity of MTA is similar to the "serotonin syndrome" observed in humans who have been on MAO inhibitors and are placed on SSRIs too quickly.

MTA may ultimately prove to be the starting material for a reagent we are trying to develop to map out the residues that line the channel in the 5-HT uptake carrier and I am sad to see it being used on the streets. I can't imagine what pleasure it might produce in users because our tests with similar compounds in rats showed the substances to have aversive or unpleasant effects.

The effect of MTA therefore must be similar to that of giving an MAO inhibitor along with Prozac, a combination that is known to be very toxic and has also led to deaths. With other amphetamines you apparently get hypertensive crises from peripheral NE release, and often malignant hyperthermia. It seems unlikely that serotonin release would do the same things, and in animal studies MTA had little direct effect on DA or NE."

A user who tried 125mg of MTA (purchased from a Dutch smartshop) described the effect as:

"not psychedelic, nor really stimulant either, neither fish nor flesh. I won't bother again and don't recommend it".

Although 4-MTA is not currently a controlled substance in Holland, the VLOS (a club for bonafide Dutch smartshops) refuse to stock it because it is a completely unknown substance which has never been tested on humans - the buyers are the test group. The wholesale company which supplies 4-MTA has advertised it as being "not neurotoxic" - a completely unfounded claim.

Jeroen Burger, of VLOS, commented that:

"substances with these risks should not be sold in smart shops, especially not amongst those that are members of the VLOS. We have therefore warned the distributor to stop producing/selling MTA or they will be banned from the VLOS, as will the smart shops that will keep selling MTA. We hope this will make MTA disappear before it gets too popular."

4-MTA produces no colour change in a Marquis reagent test.

More details of the chemical structure of this substance can be found on the London Toxicology Group website.

19 November 1998