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From: (Bruce Hamilton)
Subject: Thalidomide - was Re: When mistakes are made
Date: Sun, 05 May 1996 05:06:42 GMT

carl@SOL1.GPS.CALTECH.EDU (Carl J Lydick) wrote:

>In article <...>, (John Bates) writes:
>=Pharmaceutical development is littered with examples of compounds which have made
>=it to market ... and have been prescribed to man ... only to reveal serious toxicity.
>=Thalidomide is of course one of the earliest well documented example,

>Sometimes, of course, mistakes are made because someone's just too lazy to
>check his premises before making a decision.  For example, John Bates obviously
>prefers urban myth to facts, at least with respect to Thalidomide.  Y'see,
>Thalidomide is not, despite popular myth, a teratogen.  A different isomer of
>the compound is.  The problem with Thalidomide was that a company manufacturing
>the drug decided to use an alternate synthetic pathway, and their quality
>control measures didn't detect the fact that the teratogenic isomer was being
>produced in significant quantities in their new process.

Dear Carl,

I know you were trying so hard to avoid invective and venom, so I suppose
the strain was so much that you didn't realise that you could also have been
less lazy and checked before responding. I've posted the following several
times over the last few years and you obviously weren't reading those

" It is frequently suggested that the tragic birth defects caused by the
sedative-hypnotic thalidomide might have been avoided if it had been used as a
single enantiomer rather than the racemate marketed in the early 1960s.
However, this widely quoted ' fact ' has no basis as thalidomide is optically
unstable in solution; the pure isomers of thalidomide racemise by the opening
of the phthalimide ring [ shown but I'm not drawing the structures ], with
half-lives of 4-5 hours in buffer at pH 7.4 and less than 10 minutes in the

As a result, it is impossible to draw any conclusions from the toxicologically
rather dubious animal studies cited to support the conclusion, since after
administration of either enantiomer, in a very short time the other enantiomer
will be present in considerable quantity "

" 'Chiral Pharmacology' and the Regulation of New Drugs "
John Caldwell
Chemistry and Industry   6 March 1995 p.176-179

Obviously, the above knowledge also could impact on the credibility of the
original studies that allegedly showed that the pure enantiomer
was safe.....

               Bruce Hamilton

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