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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 8 of 8. This is the beginning of the thread.
Posted by Dr. Bob on September 29, 2002, at 2:27:57
[from http://www.dr-bob.org/babble/psycho/20020829/msgs/1176.html]
> The literature says that 10 mg. of Lexapro is equivalent to 40 mg. of Celexa. Does that mesh with people's experience? I don't understand why isolating one of two isomers would make the drug 4 times as potent rather than twice as potent. (I'm not a chemist, but I would have assumed the isomers in Celexa would have existed in a 1:1 ratio). Can someone explain this? I guess I'm suspicious that the makers of the drug wanted to claim that 10 mg. was equivalent to 40 mg so that they could point to a lower incidence of side effects, which wouldn't have been the case if 10 mg was equivalent to 20 mg.
Posted by dennison on September 29, 2002, at 22:09:20
In reply to Lexapro Dosage (vs. Celexa) « yeltom, posted by Dr. Bob on September 29, 2002, at 2:27:57
Hi --Easy answer because isomers have different stereochemistry, and in the world of drug effects stereochemistry is everything. One isomer might be preforming the total effect of the racemic ((r+s)) mixture. Sometimes each isomer has a positive effect, sometimes just one, and of course side-effects as well vary between the 2 isomers or of course could be essentially the same. In the case of celexa the ""s"" isomer was found to be the isomer which actually inhibits the serotonin reuptake while the r isomer was found to contribute more to the side-effects. .............................Now the issue of potency, Isomers can negate the effect of one another also-- so by removing one the attenuating effect of it on the other isomer is removed. Consider the more familiar ex. of dextro and levo amphetamine --dextro isomer is well known to have approx. a 4x CNS potency over the levo form. If the CNS effect was the sought after effect, the dextro isomer would be more potent and thus require a lower dose--Also by removing the l-isomer from and racemic mixture you have twice as much of the ""R"" form................. Whether Lexapro will pan out ""IN THE REAL WORLD"" remains to be seen. Since hype and gimmicks are so common in the pharmaceutical market. Ex.ssri and pre-clinical studies and the side-effect profiles,---- especially the sexual aspects -which were listed as being negliable---yet as we all know rates in 50%>>>70% range are more realistic. :):)
Posted by JLM on September 30, 2002, at 5:40:22
In reply to Re: Lexapro Dosage (vs. Celexa) « yeltom, posted by dennison on September 29, 2002, at 22:09:20
> Hi --Easy answer because isomers have different stereochemistry, and in the world of drug effects stereochemistry is everything. One isomer might be preforming the total effect of the racemic ((r+s)) mixture. Sometimes each isomer has a positive effect, sometimes just one, and of course side-effects as well vary between the 2 isomers or of course could be essentially the same. In the case of celexa the ""s"" isomer was found to be the isomer which actually inhibits the serotonin reuptake while the r isomer was found to contribute more to the side-effects. .............................Now the issue of potency, Isomers can negate the effect of one another also-- so by removing one the attenuating effect of it on the other isomer is removed. Consider the more familiar ex. of dextro and levo amphetamine --dextro isomer is well known to have approx. a 4x CNS potency over the levo form. If the CNS effect was the sought after effect, the dextro isomer would be more potent and thus require a lower dose--Also by removing the l-isomer from and racemic mixture you have twice as much of the ""R"" form................. Whether Lexapro will pan out ""IN THE REAL WORLD"" remains to be seen. Since hype and gimmicks are so common in the pharmaceutical market. Ex.ssri and pre-clinical studies and the side-effect profiles,---- especially the sexual aspects -which were listed as being negliable---yet as we all know rates in 50%>>>70% range are more realistic. :):)
Where is the evidence that the s-isomer is the one that causes the so called AD effect, and that the r-isomer causes SE's? I have yet to see anyone present that here. Forrest certainly cannot back that claim up with hard data.
Posted by dr. dave on October 1, 2002, at 3:47:51
In reply to Re: Lexapro Dosage (vs. Celexa) « yeltom, posted by JLM on September 30, 2002, at 5:40:22
There is a lot of evidence on this sort of thing at http://www.cipralex.ch/f/poster.html
The study
http://www.cipralex.ch/pdf/poster/sobp_500.pdf
in particular demonstrates that s-citalopram is almost entirely responsible for the SSRI activity of citalopram.In terms of evidence for r-citalopram causing side-effects - there just isn't any. An interesting thing to look at is the bit at the botttom of
http://www.cipralex.ch/pdf/poster/ifmad_01.pdf
where it says 'Escitalopram has demonstrated a lack of affinity for a very large number of receptors and binding sites - measured as citalopram'. This is followed by a list of over 50 receptors. What this shows is that this lack of activity must also be true of r-citalopram, because the results are for s- and r-citalopram combined.I keep on asking for any evidence that r-citalopram causes side-effects and no-one can come up with anything - but it gets repeated as a known fact. What can you do?
> > Where is the evidence that the s-isomer is the one that causes the so called AD effect, and that the r-isomer causes SE's? I have yet to see anyone present that here. Forrest certainly cannot back that claim up with hard data.
>
>
Posted by JLM on October 1, 2002, at 4:48:16
In reply to s-citalopram and r-citalopram » JLM, posted by dr. dave on October 1, 2002, at 3:47:51
> There is a lot of evidence on this sort of thing at http://www.cipralex.ch/f/poster.html
>
> The study
> http://www.cipralex.ch/pdf/poster/sobp_500.pdf
> in particular demonstrates that s-citalopram is almost entirely responsible for the SSRI activity of citalopram.
>
> In terms of evidence for r-citalopram causing side-effects - there just isn't any. An interesting thing to look at is the bit at the botttom of
> http://www.cipralex.ch/pdf/poster/ifmad_01.pdf
> where it says 'Escitalopram has demonstrated a lack of affinity for a very large number of receptors and binding sites - measured as citalopram'. This is followed by a list of over 50 receptors. What this shows is that this lack of activity must also be true of r-citalopram, because the results are for s- and r-citalopram combined.
>
> I keep on asking for any evidence that r-citalopram causes side-effects and no-one can come up with anything - but it gets repeated as a known fact. What can you do?
>
>
> > > Where is the evidence that the s-isomer is the one that causes the so called AD effect, and that the r-isomer causes SE's? I have yet to see anyone present that here. Forrest certainly cannot back that claim up with hard data.
> >
> >
>
>Dr. Dave thanks for that info, I will take a look at that. Very useful.
Posted by JLM on October 1, 2002, at 5:51:57
In reply to Re: s-citalopram and r-citalopram, posted by JLM on October 1, 2002, at 4:48:16
> > There is a lot of evidence on this sort of thing at http://www.cipralex.ch/f/poster.html
> >
> > The study
> > http://www.cipralex.ch/pdf/poster/sobp_500.pdf
> > in particular demonstrates that s-citalopram is almost entirely responsible for the SSRI activity of citalopram.
> >
> > In terms of evidence for r-citalopram causing side-effects - there just isn't any. An interesting thing to look at is the bit at the botttom of
> > http://www.cipralex.ch/pdf/poster/ifmad_01.pdf
> > where it says 'Escitalopram has demonstrated a lack of affinity for a very large number of receptors and binding sites - measured as citalopram'. This is followed by a list of over 50 receptors. What this shows is that this lack of activity must also be true of r-citalopram, because the results are for s- and r-citalopram combined.
> >
> > I keep on asking for any evidence that r-citalopram causes side-effects and no-one can come up with anything - but it gets repeated as a known fact. What can you do?
> >
> >
> > > > Where is the evidence that the s-isomer is the one that causes the so called AD effect, and that the r-isomer causes SE's? I have yet to see anyone present that here. Forrest certainly cannot back that claim up with hard data.
> > >
> > >
> >
> >
>
> Dr. Dave thanks for that info, I will take a look at that. Very useful.
>
>
>
>
Dr. Dave, I was doing some surfing tonight and came across some studies/info about the non-racemic version of Fluoxetine, r-fluoxetine. Apparently before research on the compound was stopped due to the danger of prolonged QT intervals, they were making the same claim that Forrest is making about s-citalopram, namely less side effects from the non-racemic mixture.Is this going to be the new trend? Was there any actual evidence that r-fluoxetine caused less side effects? It makes one wonder, how many other stereoisomer drugs we are going to see with claims off less SE's, especially in the area of psychiatric drugs.
Posted by Geezer on October 1, 2002, at 11:16:16
In reply to Re: s-citalopram and r-citalopram, posted by JLM on October 1, 2002, at 5:51:57
Dr. Dave and JLM,
I am walking on "eggshells" in response to this one. My humble opinion only...OK?
Dr. Dave - if you are seeking empirical MEDICAL evidence for the reduced incidence of SEs with Lexapro I would have to agree - there isn't any. I believe "studies" and "reports" to the contrary are subjective and anecdotal. I am not attacking the drug companies - they are the only ones providing funding for studies. If we take the FDA, Sergeon Generals Office, and the National Institute of Mental Health, collectively....they represent the problem, not the solution to meaningful drug testing. Drug testing needs to be free from political/economic/moralistic/psycho-social agendas. The only private funding I know of in the US is The Stanley Foundation.
JLM,
Your comments about r-flouxetine and QT prolongation are very important! Chemically induced first degree heart block and the possibile occurrence of multifocal ectopic firing foci in the ventrical, may have lethal results - just a lot of cardiology lingo meaning the drug screwed up the hearts conduction system. It would be interesting to know WHO found this REAL SE and how. I took an experimental MAOI in the late 70s/early 80s (can't remember the name), believe it was made by Hoest(sp) in Germany. Very effective drug but rejected by the FDA due to very rare hemolitic problems. In 1999 the FDA drove Servector(sp)-a dopaminergic tricyclic into the grey market-now only available in South America (this move left some pdocs and their patients high and dry in Europe). Presently I am taking Serzone 250mg. (if the numbers are correct there is one chance in 250,000 I will need a new liver at some point). I don't consider this a real problem, I am discontinuing the drug for the simple reason it doesn't work.
Yes, I believe we will see a trend for continued non-racemic ssris in the future....(the real evidence for reduced SEs will remain lacking).
Remember.....MHO only.....no attack intended.
Good cheer
Posted by dr dave on October 2, 2002, at 12:28:44
In reply to Re: s-citalopram and r-citalopram, posted by JLM on October 1, 2002, at 5:51:57
There's a good article about stereoisomeric drugs at
http://pubs.acs.org/cen/coverstory/7940/7940chiral.htmlIt seems likely there will be more and more single enantiomers. This will either be a fantastic thing or a terrible thing, depending on the particular drug. Developing single enantiomers has huge potential to separate side-effects off from beneficial effects, which is fantastic. It can also be used to 'extend drug life cycles', which means taking more than your fair number of years' profits from a given drug.
The important thing is to keep informed and work out which is which.
> Dr. Dave, I was doing some surfing tonight and came across some studies/info about the non-racemic version of Fluoxetine, r-fluoxetine. Apparently before research on the compound was stopped due to the danger of prolonged QT intervals, they were making the same claim that Forrest is making about s-citalopram, namely less side effects from the non-racemic mixture.
>
> Is this going to be the new trend? Was there any actual evidence that r-fluoxetine caused less side effects? It makes one wonder, how many other stereoisomer drugs we are going to see with claims off less SE's, especially in the area of psychiatric drugs.
>
>
>
This is the end of the thread.
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