Serotonin syn. Why high SSRI dose is quite safe but SSRI+DXM is considered dangerous?

[aced126]

Amphetamine and MDMA primarily work as monoamine releasers, not uptake inhibitors. Most DA uptake inhibitors lack psychostimulant activity (e.g., GBR 12909, benztropine). Cocaine and methylphenidate are unusual cases, and they may actually release dopamine through DAT.



Serotonergic transmission is regulated by autoreceptors to keep it within a very specific range. So if you block reuptake of serotonin, the cells compensate by reducing their firing rate and releasing fewer transmitter molecules per impulse. I'm not saying that there isn't any change in 5-HT transmission after acute administration of SSRIs, but the increase is substantially blunted by reduced firing and transmitter release. Acute paroxetine is certainly not perceived as being similar to MDAI or MBDB.

By what mechanism does autoreceptor activation result in reduced firing rate?

Also if this is so, then it begs the question of how cocaine and derivatives, and methylphenidate and derivates induce psychostimulant activity despite being reuptake inhibitors. Why isn't more research going into this?

 

[Renald]

Regular cough dosages shouldn't be harmful as long as you're not in the initial 1-2 weeks of initiating a new SSRI (even then the chance to catch a SS is small, but it exists).

Yeah, some docs prescribe crazy regimens sometimes.. I really don't get it why it should be so hard to get a script for ketamine to alleviate horrid treatment resistant depression and anxiety or pain when they throw out life-threatening scripts from time to time. Remember a colleague who was prescribed 150mg's of d-amphetamine per day, along with duloxetine, propranolol and ropinirole. She's having cognitive problems still now, over a year after stopping the medications. And this was from a professor at the university clinic in Switzerland.

Why probability of SS is higher when initiating SSRI therapy, not after long term usage?

 

[dopamimetic]

Think because of receptor down-regulation which occurs after some time as a result of the increased activity ... some say the effects of SSRI's are at least partially not because of generally more 5-HT but the down-regulation of some specific receptors. For example, 5-HT2C inhibits the release of norepinephrine and dopamine. Some others can cause anxiety, like 2A if I'm right. But there is also 1A which is anxiolytic ...

I've never got any benefits from 5-HT down-regulation, the SSRI's only worked for the first three-four weeks or so. The only exception was the combination of venlafaxine and DXM (don't do that). But I seem to have a shitload of atypical genetics.

 

[Bad Robot]

What cocktail are you on this xmas eve dopamimetic and how was rehab ?

 

[InterestingFACT]

Anecdotally, I've had a terrible--though not hospital worthy--reaction to just 30mg DXM alongside an SSRI. Nausea, piercing headache, feverish, felt extremely hot and uncomfortable, etc. etc.

Though this perhaps doesn't say overly much, as I seem to be hyper-sensitive to the stuff--100mg (so... Double the recommended dose, taken by accident) of the polistyrex one night left me in a drunken stupor for more than 2 days. I had to have an awkward conversation with my chemistry professor the next morning explaining why I wasn't in a fit state to take my exam.

But I've also had a girlfriend (who was on a high dose of Prozac, which she'd been taking for years, react poorly to just ~20mg of the stuff.

 

[dopamimetic]

The metabolism of DXM is heavily dependent on the CYP2D6 enzyme and its activity varies by the factor of ten between individuals if I'm right. Fluoxetine / Prozac is a very potent inhibitor of this enzyme too. This could suggest that you, InterestingFACT might have a rather low 2D6 activity- this is nothing to worry about, but it's something to consider when taking various drugs. Did you ever take codeine? That's too dependent on 2D6, but it requires it to become active so if you're a 'poor metabolizer' then you'll need higher dosages of codeine and I know of someone who was on fluoxetine and didn't get any effects from codeine, not even cough suppression at 50+ mg's.