SSRIs and 5-HT2B agonism.

[LiquidNebula]

So,i was reading about 5-HT2B agonism and how it causes valvulopathy when chronic and came across this recent study:http://www.ncbi.nlm.nih.gov/pubmed/25342944

Apart from the potential therapeutic effects for depression,does this mean that they can lead to cardiac hypertrophy and fibrosis ?

 

[DL-ark]

5-HT2B agonism is incredibly cardiotoxic, this is quite proven and established as fact, this is what the fen-phen disaster was all about.

 

[Black]

how toxic a substance really is depends on multiple factors, not the least of which is efficacy at 5-ht2b. some drugs like ergotamine are 5-ht2b agonists, but only rarely lead to valvulopathy.

 

[serotonin2A]

It doesn't necessarily mean that SSRIs and other drugs that increase plasma 5-HT levels will produce valvulopathy. As far as I am aware, all the agents known to produce valvulopathy in humans are direct 5-HT2B agonists. Although 5-HT itself can produce similar effects via 5-HT2B, it's not clear that SSRIs and serotonin releasing drugs can increase plasma 5-HT to levels sufficient to induce valvulopathy. I suspect direct agonists would be much more likely to produce the effect because dose and efficacy are theoretically the only factors that limit how much they can activate 5-HT2B, whereas the concentration of 5-HT in plasma is constrained by a number of factors.

 

[endotropic]

It doesn't necessarily mean that SSRIs and other drugs that increase plasma 5-HT levels will produce valvulopathy. As far as I am aware, all the agents known to produce valvulopathy in humans are direct 5-HT2B agonists. Although 5-HT itself can produce similar effects via 5-HT2B, it's not clear that SSRIs and serotonin releasing drugs can increase plasma 5-HT to levels sufficient to induce valvulopathy. I suspect direct agonists would be much more likely to produce the effect because dose and efficacy are theoretically the only factors that limit how much they can activate 5-HT2B, whereas the concentration of 5-HT in plasma is constrained by a number of factors.

That sounds reasonable, considering fluoxetine has been around for ~40 years now and we haven't seen a rash of Prozac related valvular disorders. On the other hand the report in the OP says that SSRI's across the board are direct 5-HT2B agonists, so I'll have to go back and look more closely at that one.