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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 6 of 6. This is the beginning of the thread.
Posted by SalArmy4me on July 2, 2001, at 0:01:00
I heard on a Grand Rounds at Univ. of CA, Los Angeles that paroxetine inhibits norepinephrine 40%. Could that be true? I know that Citalopram has no action on norepinephrine, though.
Posted by Mitch on July 2, 2001, at 12:23:00
In reply to Just how much do the SSRIs inhibit norepinephrine?, posted by SalArmy4me on July 2, 2001, at 0:01:00
Sal, I doubt that. My pdoc showed me a chart that listed all of the SSRI's and all the reuptake pump affinities. From what I remember in order of affinity for NE reuptake pumps Prozac had the most affinity with Luvox/Zoloft in the middle and Celexa/Paxil with the least affinity.
Zoloft had a modest affinity for DA reuptake inhibition and Paxil had a modest affinity for ACH reuptake inhibition.Mitch
> I heard on a Grand Rounds at Univ. of CA, Los Angeles that paroxetine inhibits norepinephrine 40%. Could that be true? I know that Citalopram has no action on norepinephrine, though.
Posted by Cam W. on July 2, 2001, at 19:46:55
In reply to Just how much do the SSRIs inhibit norepinephrine?, posted by SalArmy4me on July 2, 2001, at 0:01:00
Sal - Paroxetine (Paxil™) is the SSRI with the most noradrenergic activity (via reuptake blockade). It inhibits both the reuptake of serotonin and norepinephrine. This is probably why it's side effect profile is slightly different from other SSRIs. So, Paxil doesn't inhibit norepinephrine, but inhibits norepinephrine reuptake; and this reuptake is inhibited by 40% of baseline (which really is not that potent). This 40% blockade would be at a specfic dosage (blood concentration) and at a particular time in therapy (single dosing v. multiple dosing v. steady state). The norepinephrine action of Paxil is probably not all that important clinically (but there have been those who do think it is important), but can add to the secondary side effects or ease some of the serotonergic start-up side effects. - Cam
Posted by Mitch on July 3, 2001, at 0:12:11
In reply to Re: Just how much do the SSRIs inhibit norepinephrine? » SalArmy4me, posted by Cam W. on July 2, 2001, at 19:46:55
Cam W.
The charts I saw adjusted for differing potency with respect to selectivity of the differing SSRI's. Paxil has the highest *potency* for blocking serotonin reuptake. So, it's activity at NE reuptake pumps may appear more active relative to the other SSRi's.
Mitch> Sal - Paroxetine (Paxil™) is the SSRI with the most noradrenergic activity (via reuptake blockade). It inhibits both the reuptake of serotonin and norepinephrine. This is probably why it's side effect profile is slightly different from other SSRIs. So, Paxil doesn't inhibit norepinephrine, but inhibits norepinephrine reuptake; and this reuptake is inhibited by 40% of baseline (which really is not that potent). This 40% blockade would be at a specfic dosage (blood concentration) and at a particular time in therapy (single dosing v. multiple dosing v. steady state). The norepinephrine action of Paxil is probably not all that important clinically (but there have been those who do think it is important), but can add to the secondary side effects or ease some of the serotonergic start-up side effects. - Cam
Posted by Sunnely on July 3, 2001, at 20:22:53
In reply to Just how much do the SSRIs inhibit norepinephrine?, posted by SalArmy4me on July 2, 2001, at 0:01:00
The following is a comparison of concentration (nmol/L) of SSRIs needed to inhibit specific neurotransmitter uptake by half:
1. Serotonin:
Fluoxetine = 6.8; Fluvoxamine = 3.8; Sertraline = 0.19; Paroxetine = 0.29; Citalopram = 1.8
2. Dopamine:
Fluoxetine = 5000; Fluvoxamine = 42000; Sertraline = 48; Paroxetine = 81; Citalopram = 40000
3. Norepinephrine:
Fluoxetine = 370; Fluvoxamine = 620; Sertaline = 160; Paroxetine = 81; Citalopram = 6100
> I heard on a Grand Rounds at Univ. of CA, Los Angeles that paroxetine inhibits norepinephrine 40%. Could that be true? I know that Citalopram has no action on norepinephrine, though.
Posted by Mitch on July 4, 2001, at 0:55:46
In reply to Re: Just how much do the SSRIs inhibit norepinephrine? » SalArmy4me, posted by Sunnely on July 3, 2001, at 20:22:53
Sunnely,
Interesting, if you do a little math there it appears that Prozac is the *least* selective for 5-HT reuptake pumps and has the most likelihood of the bunch to boost NE (no surprise-it helped my ADHD the best of the bunch). Celexa is the most selective for 5-HT reuptake inhibition. But as far as *potency* goes I am somewhat surprised-evidently sertraline (Zoloft) is somewhat more potent than paroxetine (Paxil)- I had thought Paxil more potent (for 5-HT reuptake inhibition).
The next interesting batch of data that would be fascinating would be the *linearity* of the relationships of the concentration versus the blockade% of the different neurotransmitter reuptake pumps. Maybe this would explain why SSRI's have such a "flat" dose-response curve?
And possibly this would explain the narrower "therapeutic window" for AD's that inhibit reuptake of DA and NE (such as TCA's)?
> The following is a comparison of concentration (nmol/L) of SSRIs needed to inhibit specific neurotransmitter uptake by half:
>
> 1. Serotonin:
>
> Fluoxetine = 6.8; Fluvoxamine = 3.8; Sertraline = 0.19; Paroxetine = 0.29; Citalopram = 1.8
>
> 2. Dopamine:
>
> Fluoxetine = 5000; Fluvoxamine = 42000; Sertraline = 48; Paroxetine = 81; Citalopram = 40000
>
> 3. Norepinephrine:
>
> Fluoxetine = 370; Fluvoxamine = 620; Sertaline = 160; Paroxetine = 81; Citalopram = 6100
>
>
> > I heard on a Grand Rounds at Univ. of CA, Los Angeles that paroxetine inhibits norepinephrine 40%. Could that be true? I know that Citalopram has no action on norepinephrine, though.
This is the end of the thread.
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