SYNTHESIS: A suspension of 4.0 g LAH in 300 mL anhydrous Et2O was
stirred and heated to a gentle reflux in an inert atmosphere. There
was added 3.9 g 3,4-methylenedioxy-beta-nitrostyrene (see under BOH for
its preparation) by allowing the condensing Et2O to leach it out from
a Soxhlet thimble. After the addition was complete, the reaction
mixture was held at reflux for an additional 48 h. It was then cooled
and the excess hydride was destroyed by the cautious addition of 300
mL of 1.5 N H2SO4. When both phases were completely clear, they were
separated, and the aqueous phase washed once with 50 mL Et2O. There
was then added 100 g potassium sodium tartrate, followed by sufficient
base to bring the pH >9. This was extracted with 3x75 mL CH2Cl2, and
the solvent from these pooled extracts was removed under vacuum. The
residue was dissolved in 150 mL anhydrous Et2O and saturated with
anhydrous HCl gas. There was a heavy crystallization of
3,4-methylenedioxyphenethylamine hydrochloride (MDPEA) which weighed
3.0 g and had a mp of 212-213 °C.
DOSAGE: greater than 300 mg.
DURATION: unknown.
QUALITATIVE COMMENTS: (with 200 mg) It was taken twice at different
times in a dosage of 200 milligrams each time, without the slightest
peripheral or central effects.
(with 300 mg) My tinnitus had disappeared. Probably nothing.
EXTENSIONS AND COMMENTARY: How strange. Even more than DMPEA, this
cyclic analogue MDPEA is a potential prodrug to dopamine, and would be
a prime candidate for central activity. So why is this drug not
active? The usual reason advanced by the pharmacologists is that the
body is full of potent enzymes known as monoamine oxidases, and this
is a monoamine, and so the body simply chews away on it in an
oxidative manner, inactivating it before it ever makes it to some
target receptor.
That is the pitch given in the textbooks. Phenethylamines are subject
to easy enzymatic oxidation, hence they are not active. The presence
of an alpha-methyl group (the corresponding amphetamines) blocks the
compound from easy access to the enzyme, and since that protects them
from oxidative destruction, they are active. The oft-quoted exception
is mescaline, and even it is largely destroyed, as evidenced by the
large amount needed for activity (a fraction of a gram). Sorry, I
can't buy it. This entire book is peppered with phenethylamines that
are active at the few-milligram area. Why aren't they also destroyed
as well? The textbooks simply are not right.
MDPEA was one of the seven compounds evaluated as to toxicity and
animal behavior at the University of Michigan under contract from the
Army Chemical Center. Its Edgewood Arsenal code number was EA-1297.
The number for MDA itself was EA-1298.
The beta-hydroxy analogue of MDPEA is the ethanolamine MDE, standing
for methylenedioxyethanolamine. This is an old term, and in the more
recent literature, since 1975 certainly, MDE has been used to
represent methylenedioxyethylamphetamine. The ethanolamine compound
is discussed in the recipe for DME.
There is a family of compounds, to be discussed elsewhere, that is
called the Muni-Metro (see under METHYL-J). The simplest member is
this compound, MDPEA, and under its chemically acceptable synonym,
homopiperonylamine, it can be called RHS. Following that code, then,
the N-methyl homologue of MDPEA is METHYL-H, and it has been looked
at, clinically, as an antitussive agent. N-METHYL-MDPEA, or METHYL-H,
or N-methyl-3,4-methylenedioxyphenethylamine is effective in this role
at dosages of about 30 milligrams, but I have read nothing that would
suggest that there were any central effects. I have tried it at this
level and have found a little tightness of the facial muscles, but
there was nothing at all in the mental area.
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