Comments on 4-MTA
Related to European Fatalities in 1998
interview and personal communication
Citation: Nichols DE, Erowid Eds. "Comments on 4-MTA: Related to European Fatalities in 1998". Verified by personal communication. Erowid.org. Jul 1998. Online edition: Erowid.org/chemicals/4mta/4mta_info1.shtml
The following quote is from an interview from November 1998 just after deaths were reported in European news related to 4-MTA. The original interview has been lost, but Erowid confirmed with Dr. Nichols on June 13, 2018 that this quote is genuine. Dr. David Nichols wrote further about this exact issue in a Jan 6, 2011 article in Nature titled "Legal highs: the dark side of medicinal chemistry".
"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."