![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 24 of 24. This is the beginning of the thread.
Posted by Pacha on April 12, 2000, at 14:49:17
I went to the Doctor to get Prozac for ecstacy Neurotoxicity (but said for depression), but instead of getting Prozac I was given Cipramil (citalopram hydrobromide).
Is it the same as prozac ??? Will it prevent neurotoxicity ???
It has been proven that Prozac will fully prevent Neurotoxicity of ecstacy (MDMA).Administering Prozac (fluoxetine) up to six hours after the MDMA prevents the neurotoxic damage. We know that Prozac plugs the reuptake transporters. Since it prevents the damage even if administered six hours after the MDMA, this indicates that it is not the MDMA per se that causes the damage, but something which enters the reuptake transporters after the serotonin is depleted, most likely dopamine (see the slideshow for more details.) Without the protection of prozac, the damage seems to occur slowly over the course of a 24 hour period.
Posted by saint james on April 12, 2000, at 16:22:51
In reply to Cipramil for Neurotoxicity of ecstacy ?, posted by Pacha on April 12, 2000, at 14:49:17
> I went to the Doctor to get Prozac for ecstacy Neurotoxicity (but said for depression), but instead of getting Prozac I was given Cipramil (citalopram hydrobromide).
>
> Is it the same as prozac ??? Will it prevent neurotoxicity ???
>
>
> It has been proven that Prozac will fully prevent Neurotoxicity of ecstacy (MDMA).
>
> Administering Prozac (fluoxetine) up to six hours after the MDMA prevents the neurotoxic damage. We know that Prozac plugs the reuptake transporters. Since it prevents the damage even if administered six hours after the MDMA, this indicates that it is not the MDMA per se that causes the damage, but something which enters the reuptake transporters after the serotonin is depleted, most likely dopamine (see the slideshow for more details.) Without the protection of prozac, the damage seems to occur slowly over the course of a 24 hour period.
James here....BS ! Neither of these facts is proven. Neurotoxicity or protection from it in humans.
The tests were done on animals that showed that Prozac could counteract some short term changes (called neurotoxicity, which to me is improper)
in ANIMALS LIKE RABBITS. You cannot extrapolate
to humans. It is also STUPID to mix AD's with unknown illicits.james
Posted by LostBoyinNC on April 13, 2000, at 10:11:14
In reply to Cipramil for Neurotoxicity of ecstacy ?, posted by Pacha on April 12, 2000, at 14:49:17
> I went to the Doctor to get Prozac for ecstacy Neurotoxicity (but said for depression), but instead of getting Prozac I was given Cipramil (citalopram hydrobromide).
>
> Is it the same as prozac ??? Will it prevent neurotoxicity ???
>
>
> It has been proven that Prozac will fully prevent Neurotoxicity of ecstacy (MDMA).
>
> Administering Prozac (fluoxetine) up to six hours after the MDMA prevents the neurotoxic damage. We know that Prozac plugs the reuptake transporters. Since it prevents the damage even if administered six hours after the MDMA, this indicates that it is not the MDMA per se that causes the damage, but something which enters the reuptake transporters after the serotonin is depleted, most likely dopamine (see the slideshow for more details.) Without the protection of prozac, the damage seems to occur slowly over the course of a 24 hour period.No antidepressant is going to protect you from MDMA. In fact, nothing will protect you from MDMA. The only thing that will protect you from MDMA is to AVOID TAKING MDMA IN THE FIRST PLACE! You sound really stupid. Going to end up frying your brain with MDMA. Dont kid yourself MDMA is very dangerous. Are you prepared to end up with permanently changed brain chemistry? Well, then go ahead and do some MDMA.
If something is bad for you, why do you want to take it? Do things that build you up, not things that tear you down.
Eric
Posted by Dr. Bob on April 13, 2000, at 11:06:29
In reply to Re: Cipramil for Neurotoxicity of ecstacy ?, posted by LostBoyinNC on April 13, 2000, at 10:11:14
> No antidepressant is going to protect you from MDMA. In fact, nothing will protect you from MDMA. The only thing that will protect you from MDMA is to AVOID TAKING MDMA IN THE FIRST PLACE! You sound really stupid. Going to end up frying your brain with MDMA. Dont kid yourself MDMA is very dangerous. Are you prepared to end up with permanently changed brain chemistry? Well, then go ahead and do some MDMA.
>
> If something is bad for you, why do you want to take it? Do things that build you up, not things that tear you down.This is better, but it's unacceptable to put people down. I'm going to have to try to block you from posting any more.
Bob
Posted by Sean on April 13, 2000, at 16:38:21
In reply to Cipramil for Neurotoxicity of ecstacy ?, posted by Pacha on April 12, 2000, at 14:49:17
I've read the entire article (in Brain Research)
about the comparative effects of fluoxetine, sertraline,
Meridia, Redux, and MDMA on serotonin producing cells.It was found that *all* of these drugs produced a
characteristic change in the cells described as
"corkscrew shaped" and "swollen axons". What this
really means is unkown at the moment, but it doesn't
sound very encouraging to me.In any case, taking drugs is always an ethical trade
off with risks and benefits. This goes for both legal
and illegal drugs. Personally, I would stay away
from MDMA. On the other hand, I know people who
took gobs of the stuff when it was legal and they
seem absolutely fine. Of course they may become
depressed or prematurely senile in the future due
to lasting damage in certain brain areas. I think
the risks of MDMA are not worth the results. This
is especially true for people with a tendency towards
anxiety or depression and may already have vulnerable
neurons....Sean.
> I went to the Doctor to get Prozac for ecstacy Neurotoxicity (but said for depression), but instead of getting Prozac I was given Cipramil (citalopram hydrobromide).
>
> Is it the same as prozac ??? Will it prevent neurotoxicity ???
>
>
> It has been proven that Prozac will fully prevent Neurotoxicity of ecstacy (MDMA).
>
> Administering Prozac (fluoxetine) up to six hours after the MDMA prevents the neurotoxic damage. We know that Prozac plugs the reuptake transporters. Since it prevents the damage even if administered six hours after the MDMA, this indicates that it is not the MDMA per se that causes the damage, but something which enters the reuptake transporters after the serotonin is depleted, most likely dopamine (see the slideshow for more details.) Without the protection of prozac, the damage seems to occur slowly over the course of a 24 hour period.
Posted by saint james on April 14, 2000, at 19:05:45
In reply to Neurotoxicity - SSRI's may not be so benign..., posted by Sean on April 13, 2000, at 16:38:21
>
> I've read the entire article (in Brain Research)
> about the comparative effects of fluoxetine, sertraline,
> Meridia, Redux, and MDMA on serotonin producing cells.
>
> It was found that *all* of these drugs produced a
> characteristic change in the cells described as
> "corkscrew shaped" and "swollen axons". What this
> really means is unkown at the moment, but it doesn't
> sound very encouraging to me.
>
James here....I saw this one too, again it was on animals, and in very high doses. All it proves is that animals on high doses of these meds have changes.
james
Posted by Sean on April 14, 2000, at 19:51:39
In reply to Re: Neurotoxicity - SSRI's may not be so benign..., posted by saint james on April 14, 2000, at 19:05:45
> >
> > I've read the entire article (in Brain Research)
> > about the comparative effects of fluoxetine, sertraline,
> > Meridia, Redux, and MDMA on serotonin producing cells.
> >
> > It was found that *all* of these drugs produced a
> > characteristic change in the cells described as
> > "corkscrew shaped" and "swollen axons". What this
> > really means is unkown at the moment, but it doesn't
> > sound very encouraging to me.
> >
>
>
> James here....
>
> I saw this one too, again it was on animals, and in very high doses. All it proves is that animals on high doses of these meds have changes.
>
> jamesjames -
technically you are right, but primates and humans
have been shown (with MDMA at least) to *more* sensitive
than rats with respect to nerve damage. Given that
the rat model of depression and rat-brain synaptosomes
are used to develop antidepressants, I think these
results will eventually be shown to happen in humans.
Mammalian nerve physiology is similar at the functional
level but not the organizational level.Since the substances tested are from different drug
classes, and the only thing that links them is an
effect on serotonin, I think it is important to
find out the mechanism and perhaps fix it. It
would really suck to have the very nerve system I
already have problems with be degraded by therapy...Still takin' my zoloft though... heh heh heh,
Sean.
Posted by Cindy W on April 15, 2000, at 10:41:57
In reply to Re: Neurotoxicity - SSRI's may not be so benign..., posted by Sean on April 14, 2000, at 19:51:39
> > >
> > > I've read the entire article (in Brain Research)
> > > about the comparative effects of fluoxetine, sertraline,
> > > Meridia, Redux, and MDMA on serotonin producing cells.
> > >
> > > It was found that *all* of these drugs produced a
> > > characteristic change in the cells described as
> > > "corkscrew shaped" and "swollen axons". What this
> > > really means is unkown at the moment, but it doesn't
> > > sound very encouraging to me.
> > >
> >
> >
> > James here....
> >
> > I saw this one too, again it was on animals, and in very high doses. All it proves is that animals on high doses of these meds have changes.
> >
> > james
>
> james -
>
> technically you are right, but primates and humans
> have been shown (with MDMA at least) to *more* sensitive
> than rats with respect to nerve damage. Given that
> the rat model of depression and rat-brain synaptosomes
> are used to develop antidepressants, I think these
> results will eventually be shown to happen in humans.
> Mammalian nerve physiology is similar at the functional
> level but not the organizational level.
>
> Since the substances tested are from different drug
> classes, and the only thing that links them is an
> effect on serotonin, I think it is important to
> find out the mechanism and perhaps fix it. It
> would really suck to have the very nerve system I
> already have problems with be degraded by therapy...
>
> Still takin' my zoloft though... heh heh heh,
>
> Sean.Sean, I'd hate to end up anhedonic from my brain no longer producing serotonergic nerve cells. But, heh heh heh, I'm still taking Effexor-XR. Neurotoxicity is a risk, but so is suicide (the ultimate risk with mood disorder). Quality of life is also a consideration (would I rather have all my brain cells intact and be miserable and up to my eyeballs in crap and brain-locked with obsessions, from OCD, or would I rather have a few good years and then have swollen and cork-screw shaped axons?).
Posted by saint james on April 15, 2000, at 11:59:42
In reply to Re: Neurotoxicity - SSRI's may not be so benign..., posted by Cindy W on April 15, 2000, at 10:41:57
> >
> > Since the substances tested are from different drug
> > classes, and the only thing that links them is an
> > effect on serotonin, I think it is important to
> > find out the mechanism and perhaps fix it.James here...
If you use this logic then humans have been on sertonin agents since the 1950's (imiprimine, TCA's) with no problems.
james
Posted by Sean on April 15, 2000, at 16:21:37
In reply to Re: Neurotoxicity - SSRI's may not be so benign..., posted by saint james on April 15, 2000, at 11:59:42
> James here...
>
> If you use this logic then humans have been on sertonin agents since the 1950's (imiprimine, TCA's) with no problems.
>
> jamesjames -
i may be totally wrong on this, but i was under
the impression that the serotonin effects of TCA's
(except for amitriptyline) was very small in terms of
ratio to norepinephrine. i also believe that the
precise mechanism of TCA's on serotonin is in fact
different. You can downregulate autoreceptors,
inhibit re-uptake receptors, and God knows what
else. As i understand it, all of the drugs in
the "corkscrew" study bind the serotonin re-uptake
site a particular way, and do so with an efficiency
many times that of pervious drugs. i am under the
impression that TCA's produce the serotonin result by
a different chemical means.i think it is important to look at costs and benefits
here rather than absolutes. the benefit of these
drugs is worth it to me and i am soooo thankful to
live in an age where these drugs are available. and
yet the marketing/pharmaceutical industry side of
this equation is the source of much of the information
we get. if you look at the percentages of people
reporting sexual problems in the prozac clinical
trials (3% with libido decreased, 2% with ejaculatory
dysfunction) you *know* there is something strange
going on. The percent of people having sexual problems
with SRI's is probably closer to 50% in the real
world.i think constant questioning and vigilant oversight
of the drug industry is important. i'd like my neurons not
to be corkscrewed if the option exists. maybe soon
it will become a reality.s.
Posted by saint james on April 15, 2000, at 16:48:41
In reply to Re: Neurotoxicity - SSRI's may not be so benign..., posted by Sean on April 15, 2000, at 16:21:37
>
> > James here...
> >
> > If you use this logic then humans have been on sertonin agents since the 1950's (imiprimine, TCA's) with no problems.
> >
> > james
>
> james -
>
> i may be totally wrong on this, but i was under
> the impression that the serotonin effects of TCA's
> (except for amitriptyline) was very small in terms of
> ratio to norepinephrine.
James here....Correct, you are wrong. TCA's effect serotonin for the most part, thus accounting for the high rate of sucess. Some do have more of a nor-e effect than others. I know them well as my mood only responds to meds that effect nor-e, but most people need meds that effect 5-HT.
james
Posted by Cam W. on April 15, 2000, at 17:46:20
In reply to Re: Neurotoxicity - SSRI's may not be so benign..., posted by saint james on April 15, 2000, at 16:48:41
Sean - James is right. The TCAs differ for the amount of binding (blocking) of serotonin reuptake and norepinephrine reuptake. Some TCAs have an affinity for serotonin reuptake much more than norepinephrine reuptake (eg clomipramine) and vice versa (eg desipramine).James was also correct in stating that we has been blocking serotonin reuptake since the 1950s and have had far fewer long term problems than we see with other substances we use (eg alcohol, tobacco, stimulant laxatives, etc.).
The only thing you may be able to blame on the TCAs (and perhaps the MAOIs and even newer antidepressants) is that there seem to be an iatrogenic increase in the number of cases of bipolar disorder since the second World War. I do not know if the link has been proven, but I have heard this hypotheses bandied about at a couple of lectures that I have attended recently. The proof is shaky, at best. - Cam W.
Posted by Pacha on April 16, 2000, at 4:59:35
In reply to Cipramil for Neurotoxicity of ecstacy ?, posted by Pacha on April 12, 2000, at 14:49:17
> Administering Prozac (fluoxetine) up to six hours after the MDMA prevents the neurotoxic damage. We know that Prozac plugs the reuptake transporters. Since it prevents the damage even if administered six hours after the MDMA, this indicates that it is not the MDMA per se that causes the damage, but something which enters the reuptake transporters after the serotonin is depleted, most likely dopamine (see the slideshow for more details.) Without the protection of prozac, the damage seems to occur slowly over the course of a 24 hour period.
So your saying that an SSRI, 5-HTP, Alpha Lipic acid (for the damaging free radicals) & Vitamins will not afford enough protection against the neurotoxic effects of e.Because on a lot of Dance web-sites, this is what they recommend.
Posted by sean on April 16, 2000, at 16:36:26
In reply to Re: Neurotoxicity - SSRI's may not be so benign..., posted by saint james on April 15, 2000, at 16:48:41
> >
> > > James here...
> > >
> > > If you use this logic then humans have been on sertonin agents since the 1950's (imiprimine, TCA's) with no problems.
> > >
> > > james
> >
> > james -
> >
> > i may be totally wrong on this, but i was under
> > the impression that the serotonin effects of TCA's
> > (except for amitriptyline) was very small in terms of
> > ratio to norepinephrine.
>
>
> James here....
>
> Correct, you are wrong. TCA's effect serotonin for the most part, thus accounting for the high rate of sucess. Some do have more of a nor-e effect than others. I know them well as my mood only responds to meds that effect nor-e, but most people need meds that effect 5-HT.
>
> jameswell, I did some homework on this and TCA's and
SRI's bind different locations of the serotonin
neurons. both increase net serotonin transmission
but by different means. historical use of tricyclics
may not be indicative of chronic use of SRI's.still takin' my meds in any case!
sean
Posted by Cam W. on April 16, 2000, at 21:35:14
In reply to Re: Neurotoxicity - SSRI's may not be so benign..., posted by sean on April 16, 2000, at 16:36:26
> well, I did some homework on this and TCA's and
> SRI's bind different locations of the serotonin
> neurons. both increase net serotonin transmission
> but by different means.
>
> seanSean - I find the above to be a very interesting statement.
*Could you please supply the references to back up your claims of TCAs bind to different serotonin receptors than the SSRIs?*
I was under the impression that the TCAs bound to (and affected) mainly five different receptors (serotonin reuptake, norepinephrine reuptake, muscarinic/cholinergic, alpha-adrenergic and the histamine-H1 receptors). The SSRIs, to varying degrees also bind to some of these receptors, but not usually to an appreciable extent. I thought that the TCAs and SSRIs affected the same serotonin receptors. There are at least 15 different serotonin receptor subtypes, but I have not heard of any currently marketed antidepressant to adversely affect any of these.
If you have found some new information about TCAs bind to different serotonergic receptors, I am very much interested. This may change our thinking on the long term effects of other serotonergic drugs (eg buspirone, LSD, Imitrex, etc.).
This would be ground-breaking information that I think the whole scientific community will need to embrace. Hoping to hear from you soon.
Sincerely - Cam W.
Posted by boB on April 16, 2000, at 22:05:46
In reply to Re: Neurotoxicity - SSRI's may not be so benign..., posted by sean on April 16, 2000, at 16:36:26
> Sean wrote: "historical use of tricyclics
> may not be indicative of chronic use of SRI's.
Sean,
How could historical use of one med be indicitive of chronic use of another? Is this a typo? Did you mean to write "historical records of the effects of tricylic use might not be representative of the effects of chronic SRI use"?
boB
Posted by Scott L. Schofield on April 17, 2000, at 8:35:14
In reply to Re: SSRI's may not be so benign? - To Sean, posted by Cam W. on April 16, 2000, at 21:35:14
>
> > well, I did some homework on this and TCA's and
> > SRI's bind different locations of the serotonin
> > neurons. both increase net serotonin transmission
> > but by different means.
> >
> > sean
>
> Sean - I find the above to be a very interesting statement.
>
> *Could you please supply the references to back up your claims of TCAs bind to different serotonin receptors than the SSRIs?*
>
> I was under the impression that the TCAs bound to (and affected) mainly five different receptors (serotonin reuptake, norepinephrine reuptake, muscarinic/cholinergic, alpha-adrenergic and the histamine-H1 receptors). The SSRIs, to varying degrees also bind to some of these receptors, but not usually to an appreciable extent. I thought that the TCAs and SSRIs affected the same serotonin receptors. There are at least 15 different serotonin receptor subtypes, but I have not heard of any currently marketed antidepressant to adversely affect any of these.
>
> If you have found some new information about TCAs bind to different serotonergic receptors, I am very much interested. This may change our thinking on the long term effects of other serotonergic drugs (eg buspirone, LSD, Imitrex, etc.).
>
> This would be ground-breaking information that I think the whole scientific community will need to embrace. Hoping to hear from you soon.
>
> Sincerely - Cam W.
The receptor site for reuptake blockade is the membrane reuptake transporter protein of the presynaptic neuron. This site serves an entirely different function than those receptors usually referred to on this board. The transporter acts as a shuttle to bring the released neurotransmitter back into the interior of the presynaptic neuron so that it can be used again. If a very "sticky" molecule (drug) "sits" on the "seat" of the "shuttle" and refuses to give it up, it prevents the neurotransmitter from getting its "ride" back into the cell.I know that there are subtle differences between some of the dopamine transporters. Perhaps the same is true of serotonin reuptake transporters. My guess is that any such differences in serotonin transporter, should they exist, are not significant with respect to the actions of these drugs to inhibit reuptake. Not sure.
Although the sites on the transporter where both the neurotransmitter and drug bind are technically receptors, it may be clearer to state that they "bind to the reuptake transporter", so as not to confuse this action with those that effect neuron stimulation and regulation.
- Scott
Posted by Sean on April 17, 2000, at 12:39:41
In reply to Re: SSRI's may not be so benign? - To Sean, posted by Scott L. Schofield on April 17, 2000, at 8:35:14
Well, here's what I understand (from Cooper, Bloom,
and Roth's Biochemical Basic of Neuropharmacology):- chronic presence of SSRI's decreases the responsiveness
of the 5-HT1a autoreceptors and the function of
terminal 5-HT autoreceptors. TCA's produce no
observable change in these structures- chronic presence of TCA's increases the responsiveness
of the POST-synaptic 5-HT autoreceptorsIn each case, net 5-HT neurotransmission is increased,
so it is correct to say "TCA's affect serotonin."
But the effect is produced by an observably different
mechanism. ECT also increases the post-synaptic
sensitivity of 5-HT receptors which is interesting
in the sense that profound melancholia often responds
to TCA's or ECT but not always SSRI's.There is some evidence that TCA's with a substituted
tertiary nitrogen (amitriptyline and imipramine)
do directly bind reuptake in the way SRI's do, but
not in the proportion or degree of the SRI's.From a subjective viewpoint, having taken medications
from both classes for years, I can certainly say
that they *feel* very different in terms of the
antidepressant effect and the side effects most
people have are different.I don't mean to be stiring things up here, but I
simply do not accept the argument that historical
experience with TCA's can be used as direct evidence that
SSRI induced changes in neuron morphology are not
worthy of some measured concern. Since this entire
subject started with a person asking about MDMA
neurotoxicity, might this person now argue that because
Prozac and MDMA both generate similar neuron changes,
but since we've used TCA's for 40 years without problems
it should be fine to take MDMA?Of course not.
Perhaps what we should accept is that there is a
degree of the unkown in psychopharmacology. Since
the first generation of SSRI's were created, many
subtypes of serotonin receptors have been discovered
and cloned. Drugs which act preferentially to these
subtypes may not have the same effects as the current
generation of drugs. And then there are entire classes of
neuropeptides which await exploration, so the current
meds are like shifting, ephemeral frames in some
movie about the story of our understanding of the
brain. I think we're still in the first scene of
the film...As far as the "corscrew neurons" debacle, how would everybody
feel if scientists did NOT explore the reasons
behind it? I would be very concerned. It could be a problem
or it might not. My guess is that we simply don't
know yet.Sean.
> >
> > > well, I did some homework on this and TCA's and
> > > SRI's bind different locations of the serotonin
> > > neurons. both increase net serotonin transmission
> > > but by different means.
> > >
> > > sean
> >
> > Sean - I find the above to be a very interesting statement.
> >
> > *Could you please supply the references to back up your claims of TCAs bind to different serotonin receptors than the SSRIs?*
> >
> > I was under the impression that the TCAs bound to (and affected) mainly five different receptors (serotonin reuptake, norepinephrine reuptake, muscarinic/cholinergic, alpha-adrenergic and the histamine-H1 receptors). The SSRIs, to varying degrees also bind to some of these receptors, but not usually to an appreciable extent. I thought that the TCAs and SSRIs affected the same serotonin receptors. There are at least 15 different serotonin receptor subtypes, but I have not heard of any currently marketed antidepressant to adversely affect any of these.
> >
> > If you have found some new information about TCAs bind to different serotonergic receptors, I am very much interested. This may change our thinking on the long term effects of other serotonergic drugs (eg buspirone, LSD, Imitrex, etc.).
> >
> > This would be ground-breaking information that I think the whole scientific community will need to embrace. Hoping to hear from you soon.
> >
> > Sincerely - Cam W.
>
>
> The receptor site for reuptake blockade is the membrane reuptake transporter protein of the presynaptic neuron. This site serves an entirely different function than those receptors usually referred to on this board. The transporter acts as a shuttle to bring the released neurotransmitter back into the interior of the presynaptic neuron so that it can be used again. If a very "sticky" molecule (drug) "sits" on the "seat" of the "shuttle" and refuses to give it up, it prevents the neurotransmitter from getting its "ride" back into the cell.
>
> I know that there are subtle differences between some of the dopamine transporters. Perhaps the same is true of serotonin reuptake transporters. My guess is that any such differences in serotonin transporter, should they exist, are not significant with respect to the actions of these drugs to inhibit reuptake. Not sure.
>
> Although the sites on the transporter where both the neurotransmitter and drug bind are technically receptors, it may be clearer to state that they "bind to the reuptake transporter", so as not to confuse this action with those that effect neuron stimulation and regulation.
>
>
> - Scott
Posted by Scott L. Schofield on April 17, 2000, at 14:48:07
In reply to Re: SSRI's may not be so benign? - To Sean, posted by Sean on April 17, 2000, at 12:39:41
Dear Sean,
This is a great post.
I agree with you that it is not a good idea to extrapolate the observed phenomenology of tricyclics to the SSRIs.
I have a few questions for you. I am really not sure about this stuff - I am not trying to be argumentative.
> Well, here's what I understand (from Cooper, Bloom,
> and Roth's Biochemical Basic of Neuropharmacology):Has this book been written recently?
> - chronic presence of SSRI's decreases the responsiveness
> of the 5-HT1a autoreceptors and the function of
> terminal 5-HT autoreceptors. TCA's produce no
> observable change in these structuresAre these 5-HT1a autoreceptors presynaptic?
> - chronic presence of TCA's increases the responsiveness
> of the POST-synaptic 5-HT autoreceptorsWhat subtype of receptors are these?
Are they inhibitory? Are they somato-dendritic?
Are postsynaptic 5-HT1a autoreceptors inhibitory upon the induction of an action potential when stimulated?
Would this tend to reduce the activity of these pathways?
Do any other 5-HT receptor subtypes act as postsynaptic autoreceptors?
> In each case, net 5-HT neurotransmission is increased,
> so it is correct to say "TCA's affect serotonin."
> But the effect is produced by an observably different
> mechanism. ECT also increases the post-synaptic
> sensitivity of 5-HT receptors which is interesting
> in the sense that profound melancholia often responds
> to TCA's or ECT but not always SSRI's.> There is some evidence that TCA's with a substituted
> tertiary nitrogen (amitriptyline and imipramine)
> do directly bind reuptake in the way SRI's do, but
> not in the proportion or degree of the SRI's.How does the serotonin reuptake inhibition of chlomipramine (Anafranil) compare to the SSRIs in degree?
> I don't mean to be stiring things up here, but I
> simply do not accept the argument that historical
> experience with TCA's can be used as direct evidence that
> SSRI induced changes in neuron morphology are not
> worthy of some measured concern.I agree. Who said this anyway? This is silly.
> Perhaps what we should accept is that there is a
> degree of the unkown in psychopharmacology. Since
> the first generation of SSRI's were created, many
> subtypes of serotonin receptors have been discovered
> and cloned. Drugs which act preferentially to these
> subtypes may not have the same effects as the current
> generation of drugs. And then there are entire classes of
> neuropeptides which await exploration, so the current
> meds are like shifting, ephemeral frames in some
> movie about the story of our understanding of the
> brain. I think we're still in the first scene of
> the film...Oh yeah, big-time. But I am encouraged by what I see. Perhaps there is just a hint of light visible in the black box.
> As far as the "corscrew neurons" debacle, how would everybody
> feel if scientists did NOT explore the reasons
> behind it?What is this all about?
Thank-you for taking the time to post this stuff. I may have asked too many questions - sorry.
- Scott
Posted by Sean on April 17, 2000, at 17:46:54
In reply to Re: SSRI's may not be so benign? - To Sean, posted by Scott L. Schofield on April 17, 2000, at 14:48:07
Scott - this is a fun post! I was just a bit,
oh, less than excited about the article in Brain
Research concerning SSRI's/MDMA brain changes...> Dear Sean,
>
> This is a great post.
>
> I agree with you that it is not a good idea to extrapolate the observed phenomenology of tricyclics to the SSRIs.
>
> I have a few questions for you. I am really not sure about this stuff - I am not trying to be argumentative.
>
> > Well, here's what I understand (from Cooper, Bloom,
> > and Roth's Biochemical Basic of Neuropharmacology):
>
> Has this book been written recently?It's the seventh addition, 1996. I'm sure some
things have changed since then.
>
> > - chronic presence of SSRI's decreases the responsiveness
> > of the 5-HT1a autoreceptors and the function of
> > terminal 5-HT autoreceptors. TCA's produce no
> > observable change in these structures
>
> Are these 5-HT1a autoreceptors presynaptic?I believe so. Somatodendritic.
>
> > - chronic presence of TCA's increases the responsiveness
> > of the POST-synaptic 5-HT autoreceptors
>
> What subtype of receptors are these?
>
> Are they inhibitory? Are they somato-dendritic?They are not somatodendritic. I think they are
not inhibitory in the “re-uptake” sense, but are kind
of like the "end target" of synaptic transmissions. My
understanding is that by increasing the sensitivity
and turnover on the "receiving" end (up regulation?)
that the equilibrium of the autoreceptors is disturbed,
which then causes a homeostatic shift in serotonin
production and a net increase in transmission.But the SSRI's, in my crude understanding, increase
serotonin more directly by down regulating re-uptake
and making more serotonin available. This is closer
to what MAOI's do and probably explains the similarity
of sexual side effects and specific disorders which
respond well to both classes of drugs.
> Are postsynaptic 5-HT1a autoreceptors inhibitory
upon the induction of an action potential
when stimulated?I can't tell from this book. What would this mean?
> Would this tend to reduce the activity of these pathways?
Don't know. My guess is that by having a drug
clogging-up pre-synaptic receptors a chronic basis,
the production and genetics of serotonin nerves are
altered and give rise to the changes in morphology
described in the Brain Research article.> Do any other 5-HT receptor subtypes act as
postsynaptic autoreceptors?I don't know. There are at least 15 different subtypes, probably
more as serotonin receptors are very heterogeneous. I’m still
learning about this stuff. It’s pretty arcane.>
> > In each case, net 5-HT neurotransmission is increased,
> > so it is correct to say "TCA's affect serotonin."
> > But the effect is produced by an observably different
> > mechanism. ECT also increases the post-synaptic
> > sensitivity of 5-HT receptors which is interesting
> > in the sense that profound melancholia often responds
> > to TCA's or ECT but not always SSRI's.
>
> > There is some evidence that TCA's with a substituted
> > tertiary nitrogen (amitriptyline and imipramine)
> > do directly bind reuptake in the way SRI's do, but
> > not in the proportion or degree of the SRI's.
>
> How does the serotonin reuptake inhibition
of chlomipramine (Anafranil) compare to the
SSRIs in degree?I had this chart at one point which listed serotonin
affinity between a number of antidepressants across
classes. I can't remember if Anafrinil was on there.
I do remember the SRI’s being many hundreds of
times more potent at blocking re-uptake. I think
some were many thousands of times more powerful.
>
> > I don't mean to be stiring things up here, but I
> > simply do not accept the argument that historical
> > experience with TCA's can be used as direct evidence that
> > SSRI induced changes in neuron morphology are not
> > worthy of some measured concern.
>
> I agree. Who said this anyway? This is silly.
???
> > Perhaps what we should accept is that there is a
> > degree of the unkown in psychopharmacology. Since
> > the first generation of SSRI's were created, many
> > subtypes of serotonin receptors have been discovered
> > and cloned. Drugs which act preferentially to these
> > subtypes may not have the same effects as the current
> > generation of drugs. And then there are entire classes of
> > neuropeptides which await exploration, so the current
> > meds are like shifting, ephemeral frames in some
> > movie about the story of our understanding of the
> > brain. I think we're still in the first scene of
> > the film...
>
> Oh yeah, big-time. I am encouraged by what
I see. Perhaps there is just a hint of light visible
in the black box.Yes. We live in exciting times and I’m very thankful
for it. The black box is an interesting metaphor
for both depression and what we don't know about
the brain...
>
> > As far as the "corscrew neurons" debacle, how would everybody
> > feel if scientists did NOT explore the reasons
> > behind it?
>
> What is this all about?
Did you see the Brain Research paper? I can dig
it up off the web and send it if you want.Thanks for your interest in this stuff. It is super
abstruse, but somehow therapeutic for me. It helps
organize my “secondary suffering” around medication
issues. I want to know all I can, from my personal history
to my genetic background. Every little bit helps...
>
Posted by reed houle on January 23, 2001, at 11:38:47
In reply to Neurotoxicity - SSRI's may not be so benign..., posted by Sean on April 13, 2000, at 16:38:21
I am looking for information on Ecstacy, preferably information on chemical structure and effects on the neurological system. Any help with where I can find information on this, or if anyone is willing to share information that they have I would greatly appreciate it.
-Reed Houle
Posted by stjames on January 23, 2001, at 12:18:14
In reply to MDMA, posted by reed houle on January 23, 2001, at 11:38:47
> I am looking for information on Ecstacy,
James here.....
Try http://www.erowid.org/psychoactives/psychoactives.shtml and http://www.erowid.org/library/books_online/pihkal/pihkal.shtml and www.maps.org
James
Posted by Reed Houle on January 24, 2001, at 16:50:34
In reply to Re: MDMA, posted by stjames on January 23, 2001, at 12:18:14
>
> James here.....
>
> Try http://www.erowid.org/psychoactives/psychoactives.shtml and http://www.erowid.org/library/books_online/pihkal/pihkal.shtml and www.maps.org
>
> JamesExcellent site, thanks for your help.
-Reed
Posted by mtdew on November 18, 2003, at 16:38:19
In reply to Neurotoxicity - SSRI's may not be so benign..., posted by Sean on April 13, 2000, at 16:38:21
All,
Here is the reference for the article Sean mentions:
Comparative study of fluoxetine, sibutramine, sertraline and dexfenfluramine on the morphology of serotonergic nerve terminals using serotonin immunohistochemistry
Brain Research, Volume 858, Issue 1, 6 March 2000, Pages 92-105
Madhu Kalia, James P. O'Callaghan, Diane B. Miller and Michael KramerIt can be purchased for $30 from www.sciencedirect.com. Well worth the money, I think.
Neal
>
> I've read the entire article (in Brain Research)
> about the comparative effects of fluoxetine, sertraline,
> Meridia, Redux, and MDMA on serotonin producing cells.
>
> It was found that *all* of these drugs produced a
> characteristic change in the cells described as
> "corkscrew shaped" and "swollen axons". What this
> really means is unkown at the moment, but it doesn't
> sound very encouraging to me.
>
> In any case, taking drugs is always an ethical trade
> off with risks and benefits. This goes for both legal
> and illegal drugs. Personally, I would stay away
> from MDMA. On the other hand, I know people who
> took gobs of the stuff when it was legal and they
> seem absolutely fine. Of course they may become
> depressed or prematurely senile in the future due
> to lasting damage in certain brain areas. I think
> the risks of MDMA are not worth the results. This
> is especially true for people with a tendency towards
> anxiety or depression and may already have vulnerable
> neurons....
>
> Sean.
>
>
>
>
>
>
> > I went to the Doctor to get Prozac for ecstacy Neurotoxicity (but said for depression), but instead of getting Prozac I was given Cipramil (citalopram hydrobromide).
> >
> > Is it the same as prozac ??? Will it prevent neurotoxicity ???
> >
> >
> > It has been proven that Prozac will fully prevent Neurotoxicity of ecstacy (MDMA).
> >
> > Administering Prozac (fluoxetine) up to six hours after the MDMA prevents the neurotoxic damage. We know that Prozac plugs the reuptake transporters. Since it prevents the damage even if administered six hours after the MDMA, this indicates that it is not the MDMA per se that causes the damage, but something which enters the reuptake transporters after the serotonin is depleted, most likely dopamine (see the slideshow for more details.) Without the protection of prozac, the damage seems to occur slowly over the course of a 24 hour period.
>
>
This is the end of the thread.
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