Question about how SSRIs "work"

Ok, so I know that they act like barriers by keeping serotonin/dopamine stuck in the synapse (space between neurons) for longer than normal.

They do that by preventing the reuptake pump from doing its job of recycling any unused serotonin/dopamine. God created that pump for a reason--so that serotonin/dopamine wouldn't be sitting in the synapse for too long.

So, my question is, does the higher the dosage mean that the "barrier" that blocks said reputake pump block more serotonin/dopamine? In other words, does the "barrier" get stronger/larger as you increase the dose?

[aberdeen]

Originally Posted by ElVito1981

Ok, so I know that they act like barriers by keeping serotonin/dopamine stuck in the synapse (space between neurons) for longer than normal.

They do that by preventing the reuptake pump from doing its job of recycling any unused serotonin/dopamine. God created that pump for a reason--so that serotonin/dopamine wouldn't be sitting in the synapse for too long.

So, my question is, does the higher the dosage mean that the "barrier" that blocks said reputake pump block more serotonin/dopamine? In other words, does the "barrier" get stronger/larger as you increase the dose?

If you increase your dose, I picture it like there are simply more "molecules" of barrier so to speak, so a greater number of pumps are blocked.

Originally Posted by aberdeen

If you increase your dose, I picture it like there are simply more "molecules" of barrier so to speak, so a greater number of pumps are blocked.

Ok, but are the reputake pumps that are being affected by the SSRIs completely blocked, or are some of them partially blocked (allowing some serotonin/dopamine to get sucked back in)?

[Songbird]

Chemically, I think a receptor is either blocked or not blocked. Personally, I found the drug had more effect at higher doses, although from what I've read here that isn't the same for everyone.

I don't think even the so-called experts really know how SSRIs work. These drugs don't work immediately - they tend to make people feel worse for a week or two before they begin to have any positive effect, so the way they 'work' is likely to be through some indirect path that takes time to show up, such as the body rebalancing something else as a result of what the drug does. There are various hypotheses, but nobody knows for sure.

Originally Posted by Songbird

Chemically, I think a receptor is either blocked or not blocked.

You mean the "reputake pump", not "receptor", right?

So basically then, the higher the dose, the more pumps are blocked? Because a pump can't be partially blocked?

[jheaney1]

The receptors are shaped so that they allow a certain chemical to bind to them. It works kind of like a lock and key. SSRI have the correct key shape to fit into the receptor, but lack the rest of the molecule that would activate the receptor, thus disabling that receptor. As the dose of an SSRI goes up, there is more of the chemical circulating in the brain, blocking more receptors. Over time, the blocked receptors become inactive, even without the presence of the drug. The brain favors areas that are active over areas that are inactive. As we think, we're actually rewiring our brains in a dynamic way. It takes a while for the brain to adjust to reactivating receptors. That's why stopping cold turkey is so traumatic.

By blocking the receptor, SSRI cause more Serotonin to remain in the interneural gap. The idea that more available Serotonin changes mood stems from studies done on other drugs that act on multiple receptors. XTC, Heroine, Cocaine all act on receptors in the same way, they just have key shapes for more than one type of receptor. In the case of XTC, it stimulates the brain to dump all its stored reserves of Dopamine instead of blocking its absorption.

[Songbird]

Originally Posted by ElVito1981

You mean the "reuptake pump", not "receptor", right?

Yes, what I meant by receptor was a chemical binding site. There are all kinds of these on the surface of cells (placed in cell membranes) for various functions. Some are receptor sites for hormones and neurotransmitters, some are transport proteins, and so on. Drugs mimic the action of chemicals that occur naturally in the body. Some drugs have the same action as the natural chemical - they bind and trigger whatever it is to happen. Others bind but don't actually 'work' (due to other differences in their chemical makeup) so they act as blockers.

For more information:

http://en.wikipedia.org/wiki/Reuptake_inhibitor

[markca]

Originally Posted by jheaney1

Over time, the blocked receptors become inactive, even without the presence of the drug. The brain favors areas that are active over areas that are inactive. As we think, we're actually rewiring our brains in a dynamic way. It takes a while for the brain to adjust to reactivating receptors.

do you think these receptors can in the long term absence of the drug become active once again. your posts are fascinating , you have a great knowledge of what is going on.

[jheaney1]

I took a neurophysiology class in college, which sparked an interest later on. I'm still learning about brain function.
I think that depleted receptors can activate again, but the brain would favor building networks around the area, instead. Once an SSRI binds to a receptor and it becomes inactive, you get the short term effect of increased Serotonin between neurons. As time passes, the brain wants to restore the old functional state by absorbing the excess Serotonin. New neurons form networks with the blocked area. That may have something to do with tolerance. The brain keeps trying to connect the blocked areas with functioning receptors. Once the SSRI is removed, there is an excess of new networks absorbing Serotonin, leading to a lack of transmitter in the interneural gap. It's not until the brain can rewire again and adjust to the new, new state that you get consistent levels of Serotonin. With 100 billion neurons in the brain, there's a lot of rewiring to be done.

JHeaney1, dont' SSRIs bind to the "reuptake pumps" of the TRANSMITTING neurons, not the "receptors" of the RECEIVING neurons?

[markca]

jheaney1 , i have a question.
are you basically saying that ssris cause nerve damage.
you see i took paxil for 2 months in 95 then quit. i was a mess for some time after that. but in 98 started developing pains in hands from excessive keyboard use ...was termed chronic pain syndrome, fibromialgia, repetitive strain injury, occupational overuse syndrome...just labels ....this they believe is due to nerve damage. when nerves are damaged its very difficult for them to repair..yes they send out more dentrites to try to reestablish but things are never the same again. even now i must be very careful with typing and often use dragon speaking software to type.
i guess my question is ...do you think my nerve damage in 98 was in fact originated in 95 from 2 months of paxil use which damaged nerves and set this whole saga off.?
curious.

[Songbird]

Originally Posted by ElVito1981

dont' SSRIs bind to the "reuptake pumps" of the TRANSMITTING neurons, not the "receptors" of the RECEIVING neurons?

I'm not Jheaney1 - but yes, reuptake inhibitors bind to the reuptake receptors (or pumps), not the receptors of the receiving neurons. Because the reuptake of neurotransmitter is inhibited, more neurotransmitter remains in the synapse to continue triggering the receptors of the receiving neuron.

Originally Posted by markca

i guess my question is ...do you think my nerve damage in 98 was in fact originated in 95 from 2 months of paxil use which damaged nerves and set this whole saga off.?
curious.

I think this would be very unlikely. What did you mean about being a mess after that? Occasionally someone has a severe adverse reaction which can cause severe symptoms for some time afterwards. I have seen a few members here who have reported severe problems for years afterwards, but it is quite rare. SSRI use can damage nervous system function, but that is not the same thing as permanent nerve damage. The function usually improves over time as the body rebalances neurotransmitter levels and receptors.

[markca]

thanks songbird, when i say i was a mess i mean suffered wdl symptoms uncontrollable anxiety ,suicdality etc but was so ignorant back then i couldnt understand what on earth was wrong with me.
ok so nerve damage and nerve function damage are 2 different things ...i think thats what your saying ...ok so the nerve function damage from ssri will improve with time ...yet the nerve damage from keyboard overuse may in fact be permanent...
i see....well 1 out of 2 is sure better than zero out of 2 so ill take whatever i can have.
thankyou

Originally Posted by Songbird

I'm not Jheaney1 - but yes, reuptake inhibitors bind to the reuptake receptors (or pumps), not the receptors of the receiving neurons. Because the reuptake of neurotransmitter is inhibited, more neurotransmitter remains in the synapse to continue triggering the receptors of the receiving neuron.

Right, but what happens is, over time, because of the drug, the body begins to produce less serotonin/dopamine and begins to drop receptors, correct?

As a result, tolerance/withdrawal/poop-out occurs, requiring you to either keep increasing the dose to get more temporary "relief" or slowly taper off completely to allow the brain to reboot (while going through pain in the meantime).

So, in essence, SSRIs can be short term gain, for long term pain! Had I known about all this back in 1999, I never would have started!

[Songbird]

If I'd known they were this hard to get off, I never would have started.

[jheaney1]

I used receptor as a generic term for structures on neurons that react to transmitters. Some receptors are used to trigger the next neuron in the line to fire, others stimulate the absorption of transmitters.

When neurotransmitters attach to a neuron, they create a potential in that neuron. Once a tipping point is reached, that neuron fires electrically. At the other end of the neuron, neurotransmitters are released into the next gap, which creates a new potential, and the next neuron will fire. The theory behind SSRI is that having an abundance of Serotonin in the interneural gap will stimulate neurons to fire.

I don't think that an SSRI will cause nerve damage directly. It's hard to say, though, there are many cells in the body that use Serotonin as a transmitter. I do think that it can stimulate the brain to create new connections between neurons. As some receptors are blocked, other neurons extend dendrites into the area in an attempt to replicate the function of the neurons that are no longer absorbing Serotonin. These receptors are blocked in turn, which may cause more neurons to extend into the area. When the SSRI is removed, there is an over abundance of neurons ready to absorb Serotonin, leaving a scarcity of the transmitter in the interneural gap. This leads to fluctuating levels of Serotonin, and the symptoms we experience. I think the varying levels of withdrawal that people experience is related to the amount of rewiring that the brain does while on an SSRI.

[aberdeen]

Originally Posted by jheaney1

I used receptor as a generic term for structures on neurons that react to transmitters. Some receptors are used to trigger the next neuron in the line to fire, others stimulate the absorption of transmitters.

When neurotransmitters attach to a neuron, they create a potential in that neuron. Once a tipping point is reached, that neuron fires electrically. At the other end of the neuron, neurotransmitters are released into the next gap, which creates a new potential, and the next neuron will fire. The theory behind SSRI is that having an abundance of Serotonin in the interneural gap will stimulate neurons to fire.

I don't think that an SSRI will cause nerve damage directly. It's hard to say, though, there are many cells in the body that use Serotonin as a transmitter. I do think that it can stimulate the brain to create new connections between neurons. As some receptors are blocked, other neurons extend dendrites into the area in an attempt to replicate the function of the neurons that are no longer absorbing Serotonin. These receptors are blocked in turn, which may cause more neurons to extend into the area. When the SSRI is removed, there is an over abundance of neurons ready to absorb Serotonin, leaving a scarcity of the transmitter in the interneural gap. This leads to fluctuating levels of Serotonin, and the symptoms we experience. I think the varying levels of withdrawal that people experience is related to the amount of rewiring that the brain does while on an SSRI.

That would make sense. Also it makes sense that as the brain "realizes" that there are too many receptors absorbing the current level of serotonin, that it will eventually shut down some of the extra receptor sites it produced while on the med, and balance will restore itself. No wonder theres so much chaos when a drug is rapidly stopped!

[Songbird]

I believe there are also some kinds of receptors that monitor the amount of neurotransmitters so the body knows how much to make. When SSRIs cause more serotonin to sit around in the synaptic cleft, this gets detected and may cause the body to produce less serotonin. Also, cells can 'upregulate' and 'downregulate' the number of receptors in cell membranes. Some believe that the extra serotonin could eventually cause the receiving neurons to downregulate serotonin receptors. The body has all kinds of these balancing mechanisms. It is the reason why many drugs eventually cause 'tolerance' (although not all - there are some kinds of drugs that seem to remain effective when taken long term).

[jheaney1]

Originally Posted by Songbird

I believe there are also some kinds of receptors that monitor the amount of neurotransmitters so the body knows how much to make. When SSRIs cause more serotonin to sit around in the synaptic cleft, this gets detected and may cause the body to produce less serotonin. Also, cells can 'upregulate' and 'downregulate' the number of receptors in cell membranes. Some believe that the extra serotonin could eventually cause the receiving neurons to downregulate serotonin receptors. The body has all kinds of these balancing mechanisms. It is the reason why many drugs eventually cause 'tolerance' (although not all - there are some kinds of drugs that seem to remain effective when taken long term).

That's a good point. I think that most people on SSRI don't realize that they've reached tolerance because of the added numbing effect of these drugs. It wasn't until I was well into withdrawal that I realized that Paxil had stopped working as intended years before.

Does one suddenly reach tolerance, or does it slowly build up over time?

[jheaney1]

Tolerance happens slowly, but the realization that you've reached that point can come suddenly. I think tolerance happens as more and more neurons attempt to absorb the excess Serotonin. Once the number of receptors exceeds the ability of the drug to block receptors, you're left with just the numbing effect of the drug. It takes a long time for the neurons to develop and grow, so tolerance takes a long time. Since it happens slowly, you don't realize the changes that are occurring until it reaches a point that it becomes obvious to your conscious mind.

[aberdeen]

Originally Posted by jheaney1

Tolerance happens slowly, but the realization that you've reached that point can come suddenly.

Ain't that the truth! I went from slowly developing anhedonia and extreme exhaustion over time to a full blown panic out of the blue one day!

Originally Posted by jheaney1

Tolerance happens slowly, but the realization that you've reached that point can come suddenly. I think tolerance happens as more and more neurons attempt to absorb the excess Serotonin. Once the number of receptors exceeds the ability of the drug to block receptors, you're left with just the numbing effect of the drug. It takes a long time for the neurons to develop and grow, so tolerance takes a long time. Since it happens slowly, you don't realize the changes that are occurring until it reaches a point that it becomes obvious to your conscious mind.

So what you're saying is that you can be in tolerance/poop-out and still not have any emotional/psychological symptoms, and then you start to have them?

[jheaney1]

SSRI suppress self awareness as well as emotional processes. For a lot of people, it seems like they have symptoms of tolerance, but don't recognize it as tolerance. Instead, they attribute the emerging problems to other causes, pre existing conditions. That belief is reinforced by their doctor and becomes a self perpetuating cycle of tolerance/symptoms/denial. Eventually, the symptoms reach some tipping point and the patient either falls into the pharma pit or recognizes that the drug that was supposed to help them has been causing problems.