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SSRI vs MDMA Pharmacodynamics

N

n2opiates

Bluelighter
Joined
Oct 5, 2006
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Just had a quick question(s) regarding similarities/differences between SSRIs and MDMA.

I recall reading somewhere that MDMA inhibits the reuptake of serotonin as well as increasing the amount of serotonin produced. It is the latter which I am seeking clarification on.
If the latter is true, do SSRIs act the same way (inhibiting reuptake AND increasing production)?

Thanks
 
Well first I must clarify that MDMA does not increase production, it only causes the serotonin already produced and stored to be realeased and simultaneously blocks reuptake pumps. In respect to serotonegenic action it has many similarities to SSRI's. But the key difference is that MDMA also causes significant influx of dopamine and norepiniphrine. All three chemicals are also released in an ideal ratio which is why its effects are very different than many traditional amphetamines which also cause influx of the same neurotransmitters.

My area of knowledge is skimpy on SSRI's. but I believe that the main effect is exerted only from reuptake inhibition, I am not sure though please correct me if I am wrong.
 
yes, your right fastandbulbous. My mistake, I was thinking way outdated theories (or maybe just plain mixed up).

N2opiates, does this help answer your question at all?
 
yes, thank you both. maybe what i read was refering to the reverse action of the transporters and i thought it was talking about an increase in production.
tanks again for clearing that up.
 
hmm, now I am not certain but there is probably a marked increase in the rate of 5-ht production post MDMA administration. Otherwise its hard to imagine a mostly depleted serotonin supply reaching 30 - 50 percent of its normal concentration in only about a week. Can anyone else contribute some clinical evidence because I have no clue where to begin searching this topic.
 
MDMA reverses the direction of the 5HTT serotonin transporter thus pumping serotonin into the synapse directly. It also causes serotonin release indirectly by stimulating vesicle trafficking in the same way as other amphetamines (along with releasing dopamine and noradrenaline also). So MDMA releases serotonin by two seperate mechanisms, and releases the other monoamine neurotransmitters as well but to a lesser extent.

SSRIs on the other hand block the 5HTT serotonin transporter so it doesn't pump in either direction. This tends to cause serotonin levels in the synapse to build up slowly, but SSRIs also bind quite strongly to the autoinhibitory 5HT1B/1D receptors, which reduces the amount of serotonin that gets released by vesicle trafficking.

So while MDMA causes a rapid peak of serotonin in the synapse by dumping all the stored serotonin at once, SSRIs on the other hand tend to "flatten" synaptic serotonin levels by blocking reuptake but simultaneously inhibiting release.

Neither MDMA or SSRIs affect how much serotonin actually gets produced inside the neuron as this is controlled seperately, but you can boost serotonin production to some extent by taking serotonin precursors such as 5HTP.
 
hmm, now I am not certain but there is probably a marked increase in the rate of 5-ht production post MDMA administration
Click to expand...

Well serotonin is a competetive inhibitor of tryptophan hydroxylase ie negative feedback (tryptophan -> 5HTP), so low levels of serotonin will allow tryptophan hydroxylase to go flat out for a while until levels go up a bit (all the Lineweaver Burke/ Michalis Menton enzyme kinetics stuff applies here!)
 
MDMA Cell Damage resembles SSRI induced Cell Damage

Rodents treated with high doses of popular SSRI drugs develop similar damage to brain cells as those noted in MDMA users, such many serotonergic neurons taking on "hook" and "spiral" type structures, rendering them ineffecient/useless/maladapted. Search for this in any search engine.
 
Sorry if this is too off topic. MDMA has significant antinociception
effect, and I was wondering if its indirect or direct mechanisms of action possibly resemble that of the opiates in some ways (especially indirect&dopamine).

I know these links have been posted a millon and one times:
http://www.mdma.net/rats/antipain.html
 
bluecloudsky4 said:
Rodents treated with high doses of popular SSRI drugs develop similar damage to brain cells as those noted in MDMA users, such many serotonergic neurons taking on "hook" and "spiral" type structures, rendering them ineffecient/useless/maladapted. Search for this in any search engine.
Click to expand...

add to the above (which is very interesting - didn't realise) with the fact that a new anti-depresant CANNOT have follow up data on participants health past say 10 years (more like 6months) and you get yet more reason for MDMA to at least be available for clinical trials (e.g PTSD) WITHOUT moutains of red tape. :X
 
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