Posted by Shawn. T. on October 27, 2002, at 4:26:24
In reply to Re: MDMA HOW YOU THINK I GOT THIS WAY!!!!!!!!, posted by utopizen on October 26, 2002, at 18:25:53
Merck actually filed for the MDMA patent in 1912 and received it in 1914. A German chemist, Fritz Haber, first synthesized MDMA in 1891. See http://www.mdma.net/ for a massive dose of MDMA information. I'm currently helping the author with the task of describing the drug's mechanism of action in the brain. I'm eventually going to write a detailed analysis of the connections that recreational drugs have to GABAergic medium spiny neurons in the nucleus accumbens to go along with the report, but I've been sidetracked a bit recently. Note that the report mentions 5-HT2 receptors existing as GABA heteroreceptors in the VTA, although I personally find this claim to be unfounded (I'm currently trying to track down substantial evidence regarding this issue).
As for arguments that MDMA does not have neurotoxic properties in humans, they are in opposition to a significant amount of evidence to the contrary. Arguments have been made that 5-HT2A receptors mediate the neurotoxic effects of MDMA in addition to causing increases in extracellular dopamine. 5-HT1B receptors also mediate the euphoric effects of the drug, but they're not related to neurotoxicity. As far as the actual destruction of serotonin and/or dopamine neurons seen in test animals, massive repeated doses of MDMA are required to achieve these results. The real issue at hand involves damage to serotonergic axon terminals in the brain. This sort of neurotoxicity requires repetitive dosing of above average doses of MDMA. Taking MDMA on a regular basis is not a good idea; the tolerance induced requires higher doses to achieve the same effect, and therein lies the biggest danger. One thing that might not be evident is that the axons can grow back over the span of several weeks. This doesn't mean that more lasting damage is unlikely; serotonergic reinnervation patterns will be altered in a heavy MDMA user's healing brain. I strongly disagree with the notion that regular MDMA use by itself, especially when a person redoses during a single day, will not damage serotonergic axon terminals in the human brain.
As for the exact mechanism at work in MDMA neurotoxicity, the most likely explanation seems to be that excessive oxidation of free intracellular serotonin and/or dopamine plays a key role. My personal theory is that something called the vesicular monoamine transporter-2 (VMAT-2) might be involved. Researchers have found that the inhibition of VMAT-2 by methamphetamine is the primary cause of its neurotoxic effects. MDMA also inhibits VMAT-2 activity, although in a slightly different manner than METH. Decreased VMAT-2 activity caused by MDMA could result in increased levels of free intracellular dopamine and/or serotonin. High levels of intracellular monoamines result in increased oxidation in a neuron. This oxidation causes a rise in the levels of free radicals, which are known to cause cell damage. I'm personally fond of this explanation because it takes into account a key difference between MDMA and the serotonin releasing drug fenfluramine, which does not share a similar neurotoxic profile. The key difference is of course MDMA's effect on VMAT-2. Note that both drugs cause serotonin release from cells, but in a different manner. Given the similarities between METH and MDMA, there seems to be precedence for this sort of argument.
http://jpet.aspetjournals.org/cgi/content/abstract/300/3/1093
Shawn
poster:Shawn. T.
thread:125002
URL: http://www.dr-bob.org/babble/20021025/msgs/125396.html