How do SSRIs ACTUALLY work?

[vecktor]

Interesting, but odd. The other monoamines have their own releasing transporter.

an anomaly.

I don't think you have a handle on this, VMAT is embedded in the membranes of synaptic vesicles and is an uptake pump removing monoamines including SE from the cytoplasm. it exists elsewhere in the neuron too.

the idea of a releasing transporter is erroneous. DAT SERT and NET typically act as uptake pumps with the resting state having the transport site on the outside of the cell so they uptake monoamines from the cleft.

some drugs act on the monoamine reuptake proteins by causing them to reverse perhaps through indirectly phosphorylating residues in the transporter protein it seems logical that they then rest with the uptake site on the intracellular side and so when the protein cycles it can pump amines from the cytoplasm into the synapse.

the normal mode of release of monoamines (in the abscence of modulating drugs) into the synapse is by exocytosis of monoamine containing vesicles.

SERT has been used as a marker for the number of SE neurons because it is easy to label, in the same way as DAT is used as a marker for DA neurons. less SE neurons less SERT or so the theory goes. MDMA does cause the reduction in SERT density in certain areas of the brain. what this means in the great scheme of things who knows, it could be that SERT is being down regulated, or that SERT is increasingly expressed in a low affinity form for the ligand probe, or that there are less SE synapses.

 

[BilZ0r]

Id just like to add some other thoughts.

I am of the personal belief that the idea of the therapeutic lag is crap, for several reasons 1) If you get a bunch of people who have had good responses to SSRIs and you ask them how long it took for them to get an effect, they will tell you between 2 and 5 days (generally speaking). 2) SSRIs take about 2-5 days to reach peak plasma concentration. 3) If you ask GPs about people who respond to SSRIs they will tell you that the people who respond well, response soon. 4) If you get a population of depressed people, and treat them, some people get better, some people don't. If you then get the group that got better, and look at the rate at which they are getting better, you see that they start getting better within the first couple of days of treatment.

Still, as it stands, I think the neurogenesis theory is the best one.

 

[galianos8290]

For some yes for others no.......

Some people say these are wonder drugs that helped them tremendously in their lives. In my experience the side-effects were far worse than the suppossed benifits. In clinical trials they aer shown to be equally efective as a palcebo. It depends on the person who takes them I guess.

 

[Hammilton]

I don't think you have a handle on this, VMAT is embedded in the membranes of synaptic vesicles and is an uptake pump removing monoamines including SE from the cytoplasm. it exists elsewhere in the neuron too.

the idea of a releasing transporter is erroneous. DAT SERT and NET typically act as uptake pumps with the resting state having the transport site on the outside of the cell so they uptake monoamines from the cleft.

some drugs act on the monoamine reuptake proteins by causing them to reverse perhaps through indirectly phosphorylating residues in the transporter protein it seems logical that they then rest with the uptake site on the intracellular side and so when the protein cycles it can pump amines from the cytoplasm into the synapse.

the normal mode of release of monoamines (in the abscence of modulating drugs) into the synapse is by exocytosis of monoamine containing vesicles.

SERT has been used as a marker for the number of SE neurons because it is easy to label, in the same way as DAT is used as a marker for DA neurons. less SE neurons less SERT or so the theory goes. MDMA does cause the reduction in SERT density in certain areas of the brain. what this means in the great scheme of things who knows, it could be that SERT is being down regulated, or that SERT is increasingly expressed in a low affinity form for the ligand probe, or that there are less SE synapses.

Wow, I've been confused about this for a long, long time. Thanks for explaining this. The Amp - releasing - VMAT2 ligand, Cocaine - DARI - DAT ligand is what confused me.

10 minutes on wikipedia would have cleared that up!

to all you other assholes who let me go on thinking this...