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Reuptake Inhibitor Efficacy Options
 
King Tryptamine
#1 Posted : 12/4/2019 10:14:54 PM
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Hi there!

Having worked with the leaves of the wonderful and beautiful Erythroxylum coca plant over the last couple of months and exploring its ancient but marvelous medicinal, therapeutic and recreational attributes. Two thoughts came to mind.

Firstly I began to wonder as to why its plant spirit, cocaine had a greater efficacy eliciting a far superior bioactive response (e.g. antidepressant) in comparison to some of the standardized pharmaceutical antidepressants which also function as inhibitors of either SERT, NET or DAT or a varied combination of them?

Also and more largely as to why does it take so long (approx 2-4 weeks) for one of them to produce a response while the other one works virtually as soon as it hits the CNS tissue?

Any feedback on these questions, esp the latter would be greatly appreciated.

 

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burnt
#2 Posted : 12/9/2019 6:23:15 AM

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Cocaine mostly inhibits dopamine reuptake while modern antidepressants are selective seretonin reuptake inhibitors. Selective meaning they are quite specific to mainly just serotonin receptors. So that is one main difference. Cocaine produces acute euphoria but I would argue that is different then the antidepressant effects experienced with SSRI's which is more gradual. No one really knows exactly how SSRI's exhibit gradual changes in mood.
 
downwardsfromzero
#3 Posted : 12/9/2019 11:24:28 AM

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Coca leaf contains other alkaloids in addition to cocaine. Their nature and concentration vary depending on the species and variety of coca.

For example, Trujillo coca contains methylecgonine cinnamate and its dimers truxilline(IIRC).

https://en.wikipedia.org/wiki/Coca_alkaloid

And, notably: https://en.wikipedia.org...ki/Salicylmethylecgonine
Quote:
The hydroxy branch renders the molecule a QSAR of a 10-fold increase over cocaine in its binding potency for the dopamine transporter & a 52-fold enhanced affinity for the norepinephrine transporter. It also has a reduced selectivity for the serotonin transporter though only due to its greater increase at NET binding; its SERT affinity being 4-fold increased compared to cocaine. However, in overall binding affinity (not uptake inhibition) it displaces ligands better across the board than cocaine in all monoamine categories.




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― Jacques Bergier, quoting Fulcanelli
 
dragonrider
#4 Posted : 12/9/2019 5:41:07 PM

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I would not say that cocaine is a very effective antidepressant.

The word "antidepressant" does, oddly enough, not have the opposite meaning of "depressant".

"Depressant" means something like calming or sedating. "Antidepressant" means that it is effective against some depressive disorders. The opposite of antidepressant is "depressogenic".

Cocaine has the opposite effect of a depressant. But i would rather call it a depressogenic than an antidepressant. This is because it is very short lasting, gives a bit of a hangover, and does not have anything like an afterglow. It drains energy, rather than giving it.
 
 
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