Newsgroups: sci.med.pharmacy
Subject: Re: Ephedra Alkaloids versus pseudoephedrine
From: dyer@spdcc.com (Steve Dyer)
Date: Thu, 15 Jul 1999 05:58:03 GMT

In article <378D326C.65453727@worldnet.att.net>,
John W. Barron <j.w.barron@att.net> wrote:
   >Pseudoephedrine is the d,l isomer of ephedrine.

Pseudoephedrine is not racemic ephedrine.

The ephedrine molecule has 2 chiral carbons, or centers of symmetry.

A carbon atom can attach to 4 other atoms with single bonds.
When 4 distinct groups are attached to a carbon atom, the atom
is said to be chiral (or -handed), because there are two distinct
mirror-image arrangements of the 4 atoms possible, each known as
a stereoisomer:

     E                  E
     |                  |
     |                  |
A -- C  -- B       B -- C -- A
     |                  |
     |                  |
     D                  D

Just as you can't superimpose your left and right hands on top of
each other, the two isomers abstracted above can't be superimposed:
they each have a distinct 3-dimensional "shape".  Most organic
chemicals, whether synthetic or found in nature, have at least one
center of symmetry.


       OH     H                    H      H
       |      |                    |      |
       |*     |+                   |*     |+
Phe -- C  --  C -- CH3      Phe -- C  --  C -- CH3
       |      |                    |      |
       |      |                    |      |
       H      NH-- CH3             OH     NH-- CH3

Because the phenethanolamine skeleton has two centers of symmetry,
ephedrine has 4 possible stereoisomers; two of the isomers are used in
medicine: d-pseudoephedrine and l-ephedrine.  These have identical
configurations around the alpha-carbons, but the orientation of the
functional groups on the beta carbons are mirror images of each other.
(The alpha-carbon is marked with a plus sign; the beta-carbon is marked
with an asterisk.)

   >Ephedrine is the naturally occuring alkaloid in ma huang.

One of them.  Pseudoephedrine also is one of the alkaloids in Ma Huang.

   >It does have "stimulating" properties, as well as bronchodilation.
   >Pseudoephredrine has a much lower incidence of stimulating properties [sic.]
   >than does ephedrine.

And, it's claimed, more alpha-adrenergic activity and less beta-adrenergic
activity than ephedrine (though I doubt this has been taken much beyond
clinical anecdote), which explains why pseudoephedrine is used as a
nasal decongestant.  Ephedrine is virtually obsolete as a bronchodilator
in the treatment of asthma due to the rapid development of tolerance to
its effects on bronchial smooth muscle, though it lives on as a component
of many OTC asthma nostrums.

   >That is why the heads convert Sudafed to ephedrine using chemistry.

There are no illicit make-shift kitchen laboratories converting Sudafed to
ephedrine.  First, because ephedrine is itself widely available OTC in most
states, and second, because as a stimulant, it's quite unpleasant and
inferior to amphetamine and its analogues.

The -OH group on the beta carbon of both ephedrine and pseudoephedrine
can (with some effort) be reduced to a hydrogen, yielding (in both
cases) d-methamphetamine, the most desirable methamphetamine isomer.
(I like to think of this as God's joke on the DEA.)  Or the -OH can
be oxidized, yielding the phenylaminoketone known as methcathinone,
yielding a substance which is more amphetamine-like than ephedrine--like.
This is why drugstores, at the urging of the FDA and DEA, have placed signs
"voluntarily" limiting the number of bottles of Sudafed that can be
purchased at once.  (I'm not sure that this makes a big difference to biker
gangs churning out tons of illegal methamphetamine though it's a source
of befuddlement to the millions of cold and allergy sufferers who buy
Sudafed and its generics regularly.)

>Steve Schmidt wrote:
>
>> Can someone explain to me the difference between ephedra alkaloids
>> and pseudoephedrine?  The former is an extract from ma huang
>> that is touted as a stimulant in various sports supplements
>> and the latter is whats listed on products like sudafed.
>> Thank you in advance for your response.
--
Steve Dyer
dyer@ursa-major.spdcc.com

Newsgroups: sci.med.pharmacy
Subject: Re: Metabolife
From: dyer@spdcc.com (Steve Dyer)
Date: Fri, 22 Sep 2000 07:37:02 GMT

In article <FCLx5.53026$Qx4.1918685@news1.rdc1.il.home.com>,
rxempress <rxempress@home.com> wrote:
>To those of you who are not in the know... this is not a question of abuse.
>There are documented deaths out there with these products and I do not
>recommend them because I could be held liable if someone dies from a product
>recommendation I made.
>
>Does anyone out there have the current statistics of morbidity and
>mortality?  I am also sending a letter to our corporate HQ to protest this
>inclusion on our shelves.

I'm no fan of these concoctions that manage to skirt general accepted
standards of safety and efficacy thanks to Orrin's Hatch's bill that
eviscerated the FDA's power to regulate drugs when they're labelled as
"nutritional supplements", but there's nothing unusually dangerous in
these pills, unless you're also advising your customers that Sudafed can
kill.  Most deaths associated with ephedrine-containing products have
involved overdose, either in a misguided attempt to use them as amphetamine
substitutes, or they've been formulated in such a way that leads the
hapless customer to forget he's taking a rather powerful drug (such as
the so-called "Ripped Fuel" and similar bodybuilding meal-replacement
protein drinks that include ephedra alkaloids.)  You can find _candy_bars_
containing 12mg of ephedrine on the shelves of Walgreens these days,
which really shocked me!

I believe the FDA has at least a press release on its web site about
its concerns, though when I read it a while ago, it didn't seem to
have very much detail, and seemed like a lot of ominous bureaucratic
pique and muscle flexing.

There actually have been a few controlled clinical studies of ephedrine,
frequently in combination with caffeine and aspirin, that suggest it may
have some value in assisting with weight loss, and in short-term supervised
clinical settings, it appears to be safe.  Of course, that's a very different
environment than unsupervised self-medication with a witches' brew of "herbs"
that include ephedra alkaloids for an unbounded length of time in a population
very likely to have risk factors that would add to the risks of using this
drug, so I think that your advice is still sound.


--
Steve Dyer
dyer@ursa-major.spdcc.com